Pub Date : 2025-06-30DOI: 10.1109/TMBMC.2025.3584281
Ruifeng Zheng;Pit Hofmann;Pengjie Zhou;Juan A. Cabrera;Patrick Seeling;Martin Reisslein;Frank H. P. Fitzek
Molecular Communication via Diffusion (MCvD) is a viable communication paradigm for nanonetworks, particularly in fluidic biological environments where bio-nanonetworks operate. Two significant factors that degrade the MCvD signal are noise and Inter-Symbol Interference (ISI). The expected Channel Impulse Response (CIR) of MCvD exhibits a long, slowly attenuating tail due to molecular diffusion, leading to ISI and consequently limiting the data rate. The suppression of ISI and noise is crucial for enhancing the effectiveness of MCvD systems, especially at higher data rates. Although various ISI-suppression methods have been explored, they are often treated as secondary components in broader topics, such as signal detection or modulation. Moreover, most current ISI-suppression techniques subtract the estimated ISI from the total signal. In this study, we introduce a novel approach to ISI-suppression through the use of filters, which eliminate ISI without requiring an ISI estimation. We explore the principles underlying ISI-suppression filters in MCvD and propose the Anti-Noise ISI-Suppression (ANIS) filter with robust anti-noise capabilities, accompanied by a signal detection scheme tailored for MCvD scenarios afflicted by both ISI and noise. We compare our proposed ANIS filter against state-of-the-art detection approaches. The results demonstrate that our ANIS filter can effectively recover signals severely degraded by both ISI and noise.
{"title":"ANIS: Anti-Noise ISI-Suppression Filter for Molecular Communication via Diffusion","authors":"Ruifeng Zheng;Pit Hofmann;Pengjie Zhou;Juan A. Cabrera;Patrick Seeling;Martin Reisslein;Frank H. P. Fitzek","doi":"10.1109/TMBMC.2025.3584281","DOIUrl":"https://doi.org/10.1109/TMBMC.2025.3584281","url":null,"abstract":"Molecular Communication via Diffusion (MCvD) is a viable communication paradigm for nanonetworks, particularly in fluidic biological environments where bio-nanonetworks operate. Two significant factors that degrade the MCvD signal are noise and Inter-Symbol Interference (ISI). The expected Channel Impulse Response (CIR) of MCvD exhibits a long, slowly attenuating tail due to molecular diffusion, leading to ISI and consequently limiting the data rate. The suppression of ISI and noise is crucial for enhancing the effectiveness of MCvD systems, especially at higher data rates. Although various ISI-suppression methods have been explored, they are often treated as secondary components in broader topics, such as signal detection or modulation. Moreover, most current ISI-suppression techniques subtract the estimated ISI from the total signal. In this study, we introduce a novel approach to ISI-suppression through the use of filters, which eliminate ISI without requiring an ISI estimation. We explore the principles underlying ISI-suppression filters in MCvD and propose the Anti-Noise ISI-Suppression (ANIS) filter with robust anti-noise capabilities, accompanied by a signal detection scheme tailored for MCvD scenarios afflicted by both ISI and noise. We compare our proposed ANIS filter against state-of-the-art detection approaches. The results demonstrate that our ANIS filter can effectively recover signals severely degraded by both ISI and noise.","PeriodicalId":36530,"journal":{"name":"IEEE Transactions on Molecular, Biological, and Multi-Scale Communications","volume":"11 4","pages":"572-587"},"PeriodicalIF":2.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Intersymbol Interference (ISI) is one of the major bottlenecks in Molecular Communication via Diffusion (MCvD) systems resulting in degraded system performance. This paper first introduces two new families of linear channel codes to minimize the effect of ISI: linear Zero Pad Zero Start (ZPZS) and linear Zero Pad (ZP) codes, ensuring that every codeword is devoid of consecutive bit-1s. Subsequently, the ZPZS linear and ZP linear codes are combined to form a binary ZP code, aiming for a higher code rate compared to the linear ZP codes, which can be decoded with a simple Majority Location Rule (MLR) algorithm. Additionally, a linear Leading One Zero Pad (LOZP) code is proposed, which relaxes the zero padding constraints considering the placement of bit-1s in the codeword as an important metric to have an improved code rate than the ZP code. Finally, a closed-form expression is deduced to compute the expected ISI for the proposed codes and to demonstrate that the expected ISI is a function of the average bit-1 density of the codewords in a code. To compare the ISI and BER performance with average bit-1 density of the proposed codes, two types of MCvD channel are considered: (i) channel without refresh, where the previously transmitted bits persist for a longer duration and (ii) channel with refresh, where the channel is cleared after each successful reception of the message. The ISI comparison, across different sequence distributions for a given length and weight, shows that the linear LOZP code exhibits superior resilience against ISI in a channel with refresh due to the placement of bit-1s at the initial positions, whereas the ZP code performs better in channel without refresh by reducing the average bit-1 density of the code. The asymptotic upper bound of the code rate is derived for the proposed codes, which depicts that a trade-off exists between the ISI and code rate. The simulation results show that the proposed family of ZP and linear LOZP codes can improve the Bit Error Rate (BER) performance by controlling the bit-1 locations and the average bit-1 density of the code, specifically where the ISI is more pronounced over the channel noise, thus providing a better reliability compared to the conventional error correcting codes at different data rate regimes.
{"title":"ISI-Aware Code Design: A Linear Approach Toward Reliable Molecular Communication","authors":"Tamoghno Nath;Krishna Gopal Benerjee;Adrish Banerjee","doi":"10.1109/TMBMC.2025.3583543","DOIUrl":"https://doi.org/10.1109/TMBMC.2025.3583543","url":null,"abstract":"Intersymbol Interference (ISI) is one of the major bottlenecks in Molecular Communication via Diffusion (MCvD) systems resulting in degraded system performance. This paper first introduces two new families of linear channel codes to minimize the effect of ISI: linear Zero Pad Zero Start (ZPZS) and linear Zero Pad (ZP) codes, ensuring that every codeword is devoid of consecutive bit-1s. Subsequently, the ZPZS linear and ZP linear codes are combined to form a binary ZP code, aiming for a higher code rate compared to the linear ZP codes, which can be decoded with a simple Majority Location Rule (MLR) algorithm. Additionally, a linear Leading One Zero Pad (LOZP) code is proposed, which relaxes the zero padding constraints considering the placement of bit-1s in the codeword as an important metric to have an improved code rate than the ZP code. Finally, a closed-form expression is deduced to compute the expected ISI for the proposed codes and to demonstrate that the expected ISI is a function of the average bit-1 density of the codewords in a code. To compare the ISI and BER performance with average bit-1 density of the proposed codes, two types of MCvD channel are considered: (i) channel without refresh, where the previously transmitted bits persist for a longer duration and (ii) channel with refresh, where the channel is cleared after each successful reception of the message. The ISI comparison, across different sequence distributions for a given length and weight, shows that the linear LOZP code exhibits superior resilience against ISI in a channel with refresh due to the placement of bit-1s at the initial positions, whereas the ZP code performs better in channel without refresh by reducing the average bit-1 density of the code. The asymptotic upper bound of the code rate is derived for the proposed codes, which depicts that a trade-off exists between the ISI and code rate. The simulation results show that the proposed family of ZP and linear LOZP codes can improve the Bit Error Rate (BER) performance by controlling the bit-1 locations and the average bit-1 density of the code, specifically where the ISI is more pronounced over the channel noise, thus providing a better reliability compared to the conventional error correcting codes at different data rate regimes.","PeriodicalId":36530,"journal":{"name":"IEEE Transactions on Molecular, Biological, and Multi-Scale Communications","volume":"11 4","pages":"549-571"},"PeriodicalIF":2.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1109/TMBMC.2025.3581468
Alexander S. Moffett;Andrew W. Eckford
In an information-processing investment game, such as the growth of a population of organisms in a changing environment, Kelly betting maximizes the expected log rate of growth. In this paper, we show that Kelly bets are closely related to optimal single-letter codes (i.e., they can achieve the rate-distortion bound with equality). Thus, natural information processing systems with limited computational resources can achieve information-theoretically optimal performance. We show that the rate-distortion tradeoff for an investment game has a simple linear bound, and that the bound is achievable at the point where the corresponding single-letter code is optimal. This interpretation has two interesting consequences. First, we show that increasing the organism’s portfolio of potential strategies can lead to optimal performance over a continuous range of channels, even if the strategy portfolio is fixed. Second, we show that increasing an organism’s number of phenotypes (i.e., its number of possible behaviours in response to the environment) can lead to higher growth rate, and we give conditions under which this occurs. Examples illustrating the results in simplified biological scenarios are presented.
{"title":"Kelly Bets and Single-Letter Codes: Optimal Information Processing in Natural Systems","authors":"Alexander S. Moffett;Andrew W. Eckford","doi":"10.1109/TMBMC.2025.3581468","DOIUrl":"https://doi.org/10.1109/TMBMC.2025.3581468","url":null,"abstract":"In an information-processing investment game, such as the growth of a population of organisms in a changing environment, Kelly betting maximizes the expected log rate of growth. In this paper, we show that Kelly bets are closely related to optimal single-letter codes (i.e., they can achieve the rate-distortion bound with equality). Thus, natural information processing systems with limited computational resources can achieve information-theoretically optimal performance. We show that the rate-distortion tradeoff for an investment game has a simple linear bound, and that the bound is achievable at the point where the corresponding single-letter code is optimal. This interpretation has two interesting consequences. First, we show that increasing the organism’s portfolio of potential strategies can lead to optimal performance over a continuous range of channels, even if the strategy portfolio is fixed. Second, we show that increasing an organism’s number of phenotypes (i.e., its number of possible behaviours in response to the environment) can lead to higher growth rate, and we give conditions under which this occurs. Examples illustrating the results in simplified biological scenarios are presented.","PeriodicalId":36530,"journal":{"name":"IEEE Transactions on Molecular, Biological, and Multi-Scale Communications","volume":"11 3","pages":"418-434"},"PeriodicalIF":2.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1109/TMBMC.2025.3581470
Hongbin Ni;Ozgur B. Akan
Signal detection in diffusion-based molecular communication (MC) is challenged by stochastic propagation, inter-symbol interference (ISI), and rapidly varying microfluidic channels. This paper presents ART-Rx, an adaptive real-time threshold receiver that embeds a proportional–integral–derivative (PID) controller in a conceptual system-on-chip with the detection threshold updated once per symbol interval. Extensive Smoldyn and MATLAB simulations sweep the interferer molecule count, concentration-shift keying (CSK) levels, flow velocity, transmitter–receiver (Tx–Rx) distance, diffusion coefficient, and receptor binding rate. Averaged over the interferer molecule sweep, ART-Rx achieves a mean bit-error ratio (BER) of $1.8times 10^{-2}$ . Across −4 dB ≤ SNR ≤ 19 dB the BER remains below $6.0times 10^{-2}$ , and never exceeds $7.4times 10^{-2}$ for Tx–Rx distances up to $1times 10^{-2},mathrm {m}$ . The closed-loop strategy outperforms a statistical fixed-threshold detector and achieves a $2.6times $ lower BER than a prior non-machine learning (ML) baseline while retaining $mathcal {O}(1)$ operations per symbol. Gain scheduling, coupled with Ziegler—Nichols (Z–N) tuned PID gains and an integral windup clamp, preserves stability across strongly non-linear parameter regimes. These results position ART-Rx as a practical Rx front-end for small, resource-constrained Internet of Bio-Nano Things (IoBNT) nodes and implantable biosensors.
{"title":"ART-Rx: A Proportional-Integral-Derivative (PID) Controlled Adaptive Real-Time Threshold Receiver for Molecular Communication","authors":"Hongbin Ni;Ozgur B. Akan","doi":"10.1109/TMBMC.2025.3581470","DOIUrl":"https://doi.org/10.1109/TMBMC.2025.3581470","url":null,"abstract":"Signal detection in diffusion-based molecular communication (MC) is challenged by stochastic propagation, inter-symbol interference (ISI), and rapidly varying microfluidic channels. This paper presents ART-Rx, an adaptive real-time threshold receiver that embeds a proportional–integral–derivative (PID) controller in a conceptual system-on-chip with the detection threshold updated once per symbol interval. Extensive Smoldyn and MATLAB simulations sweep the interferer molecule count, concentration-shift keying (CSK) levels, flow velocity, transmitter–receiver (Tx–Rx) distance, diffusion coefficient, and receptor binding rate. Averaged over the interferer molecule sweep, ART-Rx achieves a mean bit-error ratio (BER) of <inline-formula> <tex-math>$1.8times 10^{-2}$ </tex-math></inline-formula>. Across −4 dB ≤ SNR ≤ 19 dB the BER remains below <inline-formula> <tex-math>$6.0times 10^{-2}$ </tex-math></inline-formula>, and never exceeds <inline-formula> <tex-math>$7.4times 10^{-2}$ </tex-math></inline-formula> for Tx–Rx distances up to <inline-formula> <tex-math>$1times 10^{-2},mathrm {m}$ </tex-math></inline-formula>. The closed-loop strategy outperforms a statistical fixed-threshold detector and achieves a <inline-formula> <tex-math>$2.6times $ </tex-math></inline-formula> lower BER than a prior non-machine learning (ML) baseline while retaining <inline-formula> <tex-math>$mathcal {O}(1)$ </tex-math></inline-formula> operations per symbol. Gain scheduling, coupled with Ziegler—Nichols (Z–N) tuned PID gains and an integral windup clamp, preserves stability across strongly non-linear parameter regimes. These results position ART-Rx as a practical Rx front-end for small, resource-constrained Internet of Bio-Nano Things (IoBNT) nodes and implantable biosensors.","PeriodicalId":36530,"journal":{"name":"IEEE Transactions on Molecular, Biological, and Multi-Scale Communications","volume":"11 3","pages":"435-450"},"PeriodicalIF":2.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-13DOI: 10.1109/TMBMC.2025.3579530
Taha Sajjad;Andrew W. Eckford
Biomolecules exhibit a remarkable property of transforming signals from their environment. This paper presents a communication system design using a light-modulated protein channel: Synthetic Photoisomerizable Azobenzene-regulated K+ (SPARK). Our approach involves a comprehensive design incorporating the SPARK-based receiver, encoding methods, modulation techniques, and detection processes. By analyzing the resulting communication system, we determine how different parameters influence its performance. Furthermore, we explore the potential design in terms of bioengineering and demonstrate that the data rate scales up with the number of receptors, indicating the possibility of achieving high-speed communication.
{"title":"Communication System Design Using Synthetic Photoisomerizable Azobenzene-Regulated K+ (SPARK) Channel","authors":"Taha Sajjad;Andrew W. Eckford","doi":"10.1109/TMBMC.2025.3579530","DOIUrl":"https://doi.org/10.1109/TMBMC.2025.3579530","url":null,"abstract":"Biomolecules exhibit a remarkable property of transforming signals from their environment. This paper presents a communication system design using a light-modulated protein channel: Synthetic Photoisomerizable Azobenzene-regulated K+ (SPARK). Our approach involves a comprehensive design incorporating the SPARK-based receiver, encoding methods, modulation techniques, and detection processes. By analyzing the resulting communication system, we determine how different parameters influence its performance. Furthermore, we explore the potential design in terms of bioengineering and demonstrate that the data rate scales up with the number of receptors, indicating the possibility of achieving high-speed communication.","PeriodicalId":36530,"journal":{"name":"IEEE Transactions on Molecular, Biological, and Multi-Scale Communications","volume":"11 3","pages":"451-461"},"PeriodicalIF":2.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-12DOI: 10.1109/TMBMC.2025.3574832
{"title":"IEEE Communications Society Information","authors":"","doi":"10.1109/TMBMC.2025.3574832","DOIUrl":"https://doi.org/10.1109/TMBMC.2025.3574832","url":null,"abstract":"","PeriodicalId":36530,"journal":{"name":"IEEE Transactions on Molecular, Biological, and Multi-Scale Communications","volume":"11 2","pages":"C3-C3"},"PeriodicalIF":2.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=11033153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144272804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-12DOI: 10.1109/TMBMC.2025.3574834
Yifan Chen
{"title":"Special Feature: 15th EAI International Conference on Bio-Inspired Information and Communications Technologies and 1st Asia–Pacific Workshop on Molecular Communications","authors":"Yifan Chen","doi":"10.1109/TMBMC.2025.3574834","DOIUrl":"https://doi.org/10.1109/TMBMC.2025.3574834","url":null,"abstract":"","PeriodicalId":36530,"journal":{"name":"IEEE Transactions on Molecular, Biological, and Multi-Scale Communications","volume":"11 2","pages":"234-236"},"PeriodicalIF":2.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=11033161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144272915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-12DOI: 10.1109/TMBMC.2025.3574830
{"title":"IEEE Transactions on Molecular, Biological, and Multi-Scale Communications Publication Information","authors":"","doi":"10.1109/TMBMC.2025.3574830","DOIUrl":"https://doi.org/10.1109/TMBMC.2025.3574830","url":null,"abstract":"","PeriodicalId":36530,"journal":{"name":"IEEE Transactions on Molecular, Biological, and Multi-Scale Communications","volume":"11 2","pages":"C2-C2"},"PeriodicalIF":2.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=11033151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144272953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-29DOI: 10.1109/TMBMC.2025.3565137
Elif Dilek;Vivash Naidoo;Bobin George Abraham;Saravanan Konda Mani;Kasim S. Abass;Sandhanasamy Devanesan;Mohamad S. AlSalhi;Sureka Chandrabose;Olli Yli-Harja;Akshaya Murugesan;Meenakshisundaram Kandhavelu
Cyclic adenosine 3’,5’-monophosphate (cAMP) is a versatile secondary messenger that communicates with Guanine Nucleotide Exchange Factor (EPAC) to transfer cellular signaling and regulates numerous physiological conditions. Early studies focused on measuring this communication is considered as crucial in GPCR ligand-mediated EPAC activation, where bioluminescence resonance energy transfer (BRET) sensor has been widely used to study the cAMP level in living cells. However, a BRET sensor pairing with the best brightness and photostability for detecting low levels of cAMP in single and whole-cell populations has yet to be developed. Here, we constructed a novel BRET-based cAMP biosensor with Rluc-Epac-Citrine2. A molecular communication study revealed a significant change of over 100° in the phi value for the residues Thr253, Val259, and Thr260 in the presence of cAMP, leading to strong cAMP-Epac-induced dynamics in the ternary complex. Spectrum scanning, luminescence, and fluorescence emission studies on glioblastoma multiforme (GBM) cells demonstrated closer proximity between donor and acceptor, ensuring the cAMP sensor’s activity. This sensor detects changes in endogenous cAMP levels, and the observed BRET signal can be enhanced by increasing the concentration of the substrate, coelenterazine. The sensor also efficiently detects the communication between cAMP and EPAC in live GBM cells over time. We used this sensor to assess the activation of GPR17, a potential biomarker for GBM. The activation of MDL 29,951, a GPR17 agonist, supports the sensor’s ability to detect Gi-coupled protein activation. This study also shows the feasibility of sensor readouts using inexpensive instrumentation such as plate readers and image systems. Overall, this study sheds new light on detecting cAMP communication with EPAC and GPR17 ligand-mediated EPAC in GBM cells, potentially aiding the development of precision therapies.
{"title":"Sensing Cyclic Adenosine Monophosphate and Guanine Nucleotide Exchange Factor Communication Through Rluc-Epac-Citrine2 BRET Sensor in Live GBM Cells","authors":"Elif Dilek;Vivash Naidoo;Bobin George Abraham;Saravanan Konda Mani;Kasim S. Abass;Sandhanasamy Devanesan;Mohamad S. AlSalhi;Sureka Chandrabose;Olli Yli-Harja;Akshaya Murugesan;Meenakshisundaram Kandhavelu","doi":"10.1109/TMBMC.2025.3565137","DOIUrl":"https://doi.org/10.1109/TMBMC.2025.3565137","url":null,"abstract":"Cyclic adenosine 3’,5’-monophosphate (cAMP) is a versatile secondary messenger that communicates with Guanine Nucleotide Exchange Factor (EPAC) to transfer cellular signaling and regulates numerous physiological conditions. Early studies focused on measuring this communication is considered as crucial in GPCR ligand-mediated EPAC activation, where bioluminescence resonance energy transfer (BRET) sensor has been widely used to study the cAMP level in living cells. However, a BRET sensor pairing with the best brightness and photostability for detecting low levels of cAMP in single and whole-cell populations has yet to be developed. Here, we constructed a novel BRET-based cAMP biosensor with Rluc-Epac-Citrine2. A molecular communication study revealed a significant change of over 100° in the phi value for the residues Thr253, Val259, and Thr260 in the presence of cAMP, leading to strong cAMP-Epac-induced dynamics in the ternary complex. Spectrum scanning, luminescence, and fluorescence emission studies on glioblastoma multiforme (GBM) cells demonstrated closer proximity between donor and acceptor, ensuring the cAMP sensor’s activity. This sensor detects changes in endogenous cAMP levels, and the observed BRET signal can be enhanced by increasing the concentration of the substrate, coelenterazine. The sensor also efficiently detects the communication between cAMP and EPAC in live GBM cells over time. We used this sensor to assess the activation of GPR17, a potential biomarker for GBM. The activation of MDL 29,951, a GPR17 agonist, supports the sensor’s ability to detect Gi-coupled protein activation. This study also shows the feasibility of sensor readouts using inexpensive instrumentation such as plate readers and image systems. Overall, this study sheds new light on detecting cAMP communication with EPAC and GPR17 ligand-mediated EPAC in GBM cells, potentially aiding the development of precision therapies.","PeriodicalId":36530,"journal":{"name":"IEEE Transactions on Molecular, Biological, and Multi-Scale Communications","volume":"11 3","pages":"395-404"},"PeriodicalIF":2.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=10980078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-21DOI: 10.1109/TMBMC.2025.3562765
Tho Minh Duong;Sungoh Kwon
In this paper, we propose an analysis of the transmission success probability in a Förster resonance energy transfer (FRET)-based molecular communication system. FRET is an energy transmission process between molecules in close proximity without radiation of a photon. Since FRET has low dependency on environmental factors and a relatively wide transmission range, it has become a promising means of propagation in molecular communication. However, the limited availability of current research in the literature hampers comprehensive understanding of FRET capabilities in the context of wireless communication in general and molecular communication specifically. In this paper, we model a FRET-based communication system with relays and analyze its channel characteristics. We derive a theoretical expression for the successful transmission probability of the system under on-off keying modulation and the corresponding system capacity. Our analysis shows that performance of the proposed FRET system is influenced by parameters that include the FRET rate, the intrinsic fluorescence rate, and symbol duration. Furthermore, our analysis maintains a high level of accuracy, regardless of whether the relays share the same FRET rate or possess different FRET rates. Via simulations our analysis is verified in various environments.
{"title":"Channel Characteristics of Multi-Hop FRET-Based Molecular Communication","authors":"Tho Minh Duong;Sungoh Kwon","doi":"10.1109/TMBMC.2025.3562765","DOIUrl":"https://doi.org/10.1109/TMBMC.2025.3562765","url":null,"abstract":"In this paper, we propose an analysis of the transmission success probability in a Förster resonance energy transfer (FRET)-based molecular communication system. FRET is an energy transmission process between molecules in close proximity without radiation of a photon. Since FRET has low dependency on environmental factors and a relatively wide transmission range, it has become a promising means of propagation in molecular communication. However, the limited availability of current research in the literature hampers comprehensive understanding of FRET capabilities in the context of wireless communication in general and molecular communication specifically. In this paper, we model a FRET-based communication system with relays and analyze its channel characteristics. We derive a theoretical expression for the successful transmission probability of the system under on-off keying modulation and the corresponding system capacity. Our analysis shows that performance of the proposed FRET system is influenced by parameters that include the FRET rate, the intrinsic fluorescence rate, and symbol duration. Furthermore, our analysis maintains a high level of accuracy, regardless of whether the relays share the same FRET rate or possess different FRET rates. Via simulations our analysis is verified in various environments.","PeriodicalId":36530,"journal":{"name":"IEEE Transactions on Molecular, Biological, and Multi-Scale Communications","volume":"11 3","pages":"371-383"},"PeriodicalIF":2.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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