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Sensing Cyclic Adenosine Monophosphate and Guanine Nucleotide Exchange Factor Communication Through Rluc-Epac-Citrine2 BRET Sensor in Live GBM Cells 通过Rluc-Epac-Citrine2 BRET传感器感知活GBM细胞中环腺苷单磷酸和鸟嘌呤核苷酸交换因子的通讯
IF 2.3 Q2 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-04-29 DOI: 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.
环腺苷3 ',5 ' -单磷酸(cAMP)是一种多功能的次级信使,与鸟嘌呤核苷酸交换因子(EPAC)交流,传递细胞信号并调节多种生理条件。早期的研究集中在测量这种通讯被认为是GPCR配体介导的EPAC激活的关键,其中生物发光共振能量转移(BRET)传感器已被广泛用于研究活细胞中的cAMP水平。然而,一种具有最佳亮度和光稳定性的传感器配对用于检测单细胞和全细胞群体中的低水平cAMP尚未开发。本研究以rucc - epac - citrine2为原料,构建了一种新型的基于bret的cAMP生物传感器。一项分子通讯研究表明,在cAMP存在下,Thr253、Val259和Thr260残基的phi值发生了超过100°的显著变化,导致三元配合物中cAMP- epac诱导的强烈动力学。多形性胶质母细胞瘤(GBM)细胞的光谱扫描、发光和荧光发射研究表明,供体和受体之间的距离更近,确保了cAMP传感器的活性。该传感器检测内源性cAMP水平的变化,并且可以通过增加底物coelenterazine的浓度来增强观察到的BRET信号。该传感器还可以有效地检测活GBM细胞中cAMP和EPAC之间的通信。我们使用该传感器来评估GPR17的激活,GPR17是GBM的潜在生物标志物。MDL 29,951(一种GPR17激动剂)的激活支持该传感器检测gi偶联蛋白激活的能力。这项研究也显示了传感器读出的可行性,使用廉价的仪器,如板阅读器和图像系统。总的来说,这项研究揭示了在GBM细胞中检测cAMP与EPAC和GPR17配体介导的EPAC的通信,可能有助于精确治疗的发展。
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引用次数: 0
Channel Characteristics of Multi-Hop FRET-Based Molecular Communication 基于多跳fret的分子通信信道特性研究
IF 2.3 Q2 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-04-21 DOI: 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.
本文提出了一种基于Förster共振能量传递(FRET)的分子通信系统的传输成功率分析方法。FRET是一个能量传输过程的分子之间在接近没有辐射的光子。由于FRET对环境因素的依赖性低,传输范围相对较宽,在分子通信中已成为一种很有前途的传播手段。然而,目前文献中有限的可用性研究阻碍了对FRET在一般无线通信和具体分子通信背景下的能力的全面理解。在本文中,我们建立了一个具有中继的基于fret的通信系统模型,并分析了它的信道特性。导出了开关键控调制下系统成功传输概率和相应系统容量的理论表达式。我们的分析表明,所提出的FRET系统的性能受到参数的影响,包括FRET率,本征荧光率和符号持续时间。此外,无论继电器是否具有相同的FRET速率或具有不同的FRET速率,我们的分析都保持了高水平的准确性。通过仿真,我们的分析在不同的环境中得到了验证。
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引用次数: 0
Information-Theoretic Lifetime Maximization for IoBNT-Enabled Sensing iobnt传感的信息论寿命最大化
IF 2.3 Q2 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-04-18 DOI: 10.1109/TMBMC.2025.3562353
Caglar Koca;Mustafa Ozger;Oktay Cetinkaya;Ozgur B. Akan
Internet of Things (IoT) translates the physical world into a cyber form using wireless sensors. However, these sensors often lack longevity due to their energy-constrained batteries. This limitation is particularly critical for the Internet of Bio-Nano Things (IoBNT), in which sensors usually operate within an organism with minimum opportunities for replenishment. Thus, adopting energy-efficient strategies is vital to maximize the lifetime of such sensors and ensure the reliable execution of associated applications. To address this, this letter proposes an event-driven, time-adaptive transmission scheme based on the Kullback-Leibler (KL) distance. Specifically, the KL distance is used to measure the worth of transmitting the current sensor reading, enabling the sensor to decide whether to transmit in that sampling period, thereby saving energy and extending its lifetime. Furthermore, we identify the operational regions for sensors, namely safe, unsafe, and action, depending on application-specific parameters. The design and implementation of the required circuitry are also discussed, considering the unique constraints of the IoBNT. Performance evaluation validates that the KL distance improves sensor lifetime with an acceptable information loss.
物联网(IoT)通过无线传感器将物理世界转化为网络形式。然而,这些传感器往往缺乏寿命,因为他们的能量有限的电池。这一限制对于生物纳米物联网(IoBNT)来说尤其重要,因为传感器通常在生物体内工作,补充的机会最少。因此,采用节能策略对于最大限度地延长此类传感器的使用寿命并确保相关应用的可靠执行至关重要。为了解决这个问题,本文提出了一种基于Kullback-Leibler (KL)距离的事件驱动、时间自适应传输方案。具体来说,KL距离用于测量当前传感器读数的传输值,使传感器能够决定是否在该采样周期内传输,从而节省能源并延长其使用寿命。此外,我们根据特定应用的参数确定传感器的操作区域,即安全,不安全和动作。考虑到IoBNT的独特限制,还讨论了所需电路的设计和实现。性能评估验证了KL距离在可接受的信息损失下提高了传感器寿命。
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引用次数: 0
Extending Iterated, Spatialized Prisoner’s Dilemma to Understand Multicellularity: Game Theory With Self-Scaling Players 扩展迭代的、空间化的囚徒困境以理解多细胞:具有自缩放参与者的博弈论
IF 2.4 Q2 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-04-18 DOI: 10.1109/TMBMC.2025.3562358
Lakshwin Shreesha;Federico Pigozzi;Adam Goldstein;Michael Levin
Evolutionary developmental biology, biomedicine, neuroscience, and many aspects of the social sciences are impacted by insight into forces that facilitate the merging of active subunits into an emergent collective. The dynamics of interaction between agents are often studied in game theory, such as the popular Prisoner’s Dilemma (PD) paradigm, but the impact of these models on higher scales of organization, and their contributions to questions of how agents distinguish borders between themselves and the outside world, are not clear. Here we applied a spatialized, iterated PD model to understand the dynamics of the formation of large-scale tissues (colonies that act as one) out of single cell agents. In particular, we broke a standard assumption of PD: instead of a fixed number of players which can Cooperate or Defect on each round, we let the borders of individuality remain fluid, enabling agents to also Merge or Split. The consequences of enabling agents’ actions to change the number of agents in the world result in non-linear dynamics that are not known in advance: would higher-level (composite) individuals emerge? We characterized changes in collective formation as a function of memory size of the subunits. Our results show that when the number of agents is determined by the agents’ behavior, PD dynamics favor multicellularity, including the emergence of structured cell-groups, eventually leading to one single fully-merged tissue. These larger agents were found to have higher causal emergence than smaller ones. Moreover, we observed different spatial distributions of merged connectivity vs. of similar behavioral propensities, revealing that rich but distinct structures can coexist at the level of physical structure and the space of behavioral propensities. These dynamics raise a number of interesting and deep questions about decision-making in a self-modifying system that transitions from a metabolic to a morphological problem space, and how collective intelligences emerge, scale, and pattern.
进化发育生物学、生物医学、神经科学和社会科学的许多方面都受到促进活跃亚单位合并为新兴集体的力量的影响。在博弈论中,人们经常研究代理之间的互动动态,比如流行的囚徒困境(PD)范式,但这些模型对更高规模组织的影响,以及它们对代理如何区分自身和外部世界边界问题的贡献,都不清楚。在这里,我们应用了一个空间化的迭代PD模型来了解单细胞制剂形成大规模组织(作为一个集落)的动力学。特别是,我们打破了PD的标准假设:我们让个体边界保持流动,使代理也可以合并或分裂,而不是在每个回合中固定数量的玩家可以合作或叛变。允许代理人的行为改变世界上代理人的数量的后果是导致事先不知道的非线性动态:是否会出现更高级别的(复合)个体?我们将集体形成的变化描述为亚单位记忆大小的函数。我们的研究结果表明,当药物的数量由药物的行为决定时,PD动力学倾向于多细胞性,包括结构化细胞群的出现,最终导致一个完全融合的组织。研究发现,这些较大的动因比较小的动因具有更高的因果出现率。此外,我们还观察到合并连通性与相似行为倾向的不同空间分布,揭示了丰富而独特的结构可以在物理结构和行为倾向空间层面共存。这些动态提出了许多有趣而深刻的问题,涉及从代谢问题空间过渡到形态问题空间的自我修改系统中的决策,以及集体智能如何出现、规模和模式。
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引用次数: 0
Modeling and Optimization of Insulin Injection for Type-1 Diabetes Mellitus Management 胰岛素注射治疗1型糖尿病的建模与优化
IF 2.3 Q2 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-04-09 DOI: 10.1109/TMBMC.2025.3559470
Rinrada Jadsadaphongphaibool;Dadi Bi;Christian D. Lorenz;Yansha Deng;Robert Schober
Diabetes mellitus is a global health crisis characterized by poor blood sugar regulation, impacting millions of people worldwide and leading to severe complications and mortality. Although Type 1 Diabetes Mellitus (T1DM) has a lower number of cases compared to other forms of diabetes, it is often diagnosed at a young age and requires lifelong exogenous insulin administration. In this paper, we focus on understanding the interaction of insulin and glucose molecules within the subcutaneous layer, which is crucial for blood sugar control in T1DM patients. Specifically, we propose a comprehensive model to characterize the insulin-glucose system within the subcutaneous layer, incorporating a multicellular molecular communication system. We then divide the T1DM system into insulin and glucose subsystems and derive the end-to-end expression for insulin-glucose interaction in the subcutaneous layer. We further validate the insulin-glucose interaction analysis with an agent-based simulator. As effectively managing postprandial glucose levels is crucial for individuals with T1DM to safeguard their overall health and avert short-term and long-term complications, we also derive the optimal insulin administration time based on the derived glucose response via the Lagrange multiplier and gradient descent ascent method. This allows us to explore the impact of different types of insulin and dietary management on blood sugar levels. Simulation results confirm the correctness of our proposed model and the effectiveness of our optimized effective time window for injecting insulin in individuals with T1DM.
糖尿病是一种以血糖调节不良为特征的全球性健康危机,影响着全世界数百万人,并导致严重并发症和死亡。虽然与其他形式的糖尿病相比,1型糖尿病(T1DM)的病例数较少,但它通常在年轻时被诊断出来,并且需要终生使用外源性胰岛素。在本文中,我们重点了解胰岛素和葡萄糖分子在皮下层的相互作用,这对T1DM患者的血糖控制至关重要。具体来说,我们提出了一个综合模型来表征皮下层内的胰岛素-葡萄糖系统,包括多细胞分子通信系统。然后,我们将T1DM系统划分为胰岛素和葡萄糖子系统,并推导出胰岛素-葡萄糖在皮下层相互作用的端到端表达。我们进一步验证了胰岛素-葡萄糖相互作用分析与基于代理的模拟器。由于有效控制餐后血糖水平对于T1DM患者的整体健康和避免短期和长期并发症至关重要,我们还通过拉格朗日乘数和梯度下降上升法得出了基于葡萄糖反应的最佳胰岛素给药时间。这使我们能够探索不同类型的胰岛素和饮食管理对血糖水平的影响。仿真结果证实了我们提出的模型的正确性以及我们优化的T1DM患者注射胰岛素的有效时间窗口的有效性。
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引用次数: 0
Stochastic Diffusivity With Time-Varying Trajectory in Mobile Molecular Communication: Performance Analysis and Channel Modeling 移动分子通信中具有时变轨迹的随机扩散性:性能分析和信道建模
IF 2.3 Q2 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-04-04 DOI: 10.1109/TMBMC.2025.3558109
Nihit Bhatnagar;Sandeep Joshi
This work considers a three-dimensional mobile molecular communication (MC) with intra-body disease spread applications. The communicating devices in the considered mobile MC system are point transmitters and passive spherical receiver nano-machines (NMs) with emitted information-carrying molecules following the Gaussian Brownian motion. These NMs can be used to detect the presence of disease spread and for targeted drug delivery. We propose stochastic diffusivity models for both communicating devices and information-carrying molecules. Using the stochastic diffusivity model and considering initial distance as a reference, we derive the probability density function of the relative distance between the communicating devices. We allocate the time-varying trajectory to the information-carrying molecules moving towards receiver NM and obtain its diffusivity distribution. Through the proposed stochastic diffusivity model, we characterize the mobile MC channel by channel impulse response and derive its statistical mean. We consider the discrete-time statistical channel model at a high inter-symbol interference regime and analyze the channel performance in terms of error analysis and receiver operating characteristics. We also derive the channel capacity for the considered system model. We show the degree of accuracy through root mean square error for the Poisson and Gaussian distribution models. Furthermore, the numerical results are verified through particle-based simulations.
本工作考虑了三维移动分子通讯(MC)与体内疾病传播的应用。所考虑的移动MC系统中的通信设备是点发射器和无源球形接收器纳米机(NMs),其发射的携带信息的分子遵循高斯布朗运动。这些NMs可用于检测疾病传播的存在和靶向药物递送。我们提出了通信设备和携带信息的分子的随机扩散模型。利用随机扩散率模型,以初始距离为参考,导出了通信设备间相对距离的概率密度函数。对向接收器NM方向运动的携带信息分子分配时变轨迹,得到其扩散率分布。通过提出的随机扩散率模型,利用信道脉冲响应对移动MC信道进行了表征,并推导了其统计平均值。我们考虑了高码间干扰条件下的离散时间统计信道模型,并从误差分析和接收机工作特性两方面分析了信道性能。我们还推导了所考虑的系统模型的信道容量。我们通过泊松和高斯分布模型的均方根误差来显示精度程度。并通过粒子模拟对数值结果进行了验证。
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引用次数: 0
A Joint DNA Encoding Approach Based on LZW and Arithmetic Encoding 基于LZW和算术编码的DNA联合编码方法
IF 2.4 Q2 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-04-03 DOI: 10.1109/TMBMC.2025.3556858
Zhongyang Cheng;Qiang Liu;Kun Yang
Molecular communication (MC) represents a novel approach to communication that employs nanoengineering and bioengineering technology to establish transient communication links in challenging environments. Deoxyribonucleic acid (DNA) molecular communication can transmit more and faster data than traditional molecular communication. Deoxyribonucleic acid (DNA) has been demonstrated to offer significant advantages over traditional information carriers, including its excellent storage density and structural stability, which renders it an ideal medium for information transmission. It is therefore imperative to investigate methods of increasing the data information density of DNA in order to reduce costs and enhance overall performance. LZW encoding is Lempel-Ziv–Welch encoding which creates a string table with shorter codes representing longer strings. Arithmetic coding is a compression process that involves the continuous refinement of probabilities of the input stream within an interval. A notable drawback of LZW coding is its suboptimal compression efficiency and the presence of data redundancy after dictionary mapping. Conversely, arithmetic coding attains compression efficiency that approaches the Shannon limit. In this study, we propose a novel DNA encoding method which is capable of adaptively generating coding streams in accordance with the characteristics of the stored content. The contribution of this paper is as follows: 1) A bespoke coding dictionary is constructed, which is capable of intelligently generating the corresponding coding stream in accordance with the specific characteristics of the file to be stored. 2) Utilising arithmetic coding techniques, these coding streams are converted into the final DNA sequence by means of compression techniques. Following comprehensive verification, it has been established that the information density of this encoding method is markedly superior to that of the prevailing mainstream encoding schemes.
分子通信(MC)是一种利用纳米工程和生物工程技术在复杂环境中建立瞬时通信链路的新型通信方法。脱氧核糖核酸(DNA)分子通信可以比传统的分子通信传输更多更快的数据。脱氧核糖核酸(DNA)已被证明比传统的信息载体具有显著的优势,包括其优异的存储密度和结构稳定性,使其成为信息传输的理想介质。因此,研究提高DNA数据信息密度的方法以降低成本和提高整体性能是势在必行的。LZW编码是Lempel-Ziv-Welch编码,它创建一个字符串表,用较短的代码表示较长的字符串。算术编码是一种压缩过程,它涉及在一定间隔内对输入流的概率进行连续细化。LZW编码的一个显著缺点是其次优压缩效率和字典映射后数据冗余的存在。相反,算术编码的压缩效率接近香农极限。在这项研究中,我们提出了一种新的DNA编码方法,该方法能够根据存储内容的特征自适应地产生编码流。本文的贡献如下:1)构建了一个定制编码字典,该字典能够根据待存储文件的具体特征智能生成相应的编码流。2)利用算术编码技术,通过压缩技术将这些编码流转换为最终的DNA序列。经过综合验证,该编码方法的信息密度明显优于目前主流的编码方案。
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引用次数: 0
A Novel Experimental Platform for Thermomolecular Communications 一种新型的热分子通信实验平台
IF 2.3 Q2 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-04-01 DOI: 10.1109/TMBMC.2025.3556883
Michael Gattringer;Stefan Angerbauer;Andreas Springer;Werner Haselmayr
In this work, we present a novel thermomolecular communications gateway allowing communication through the human skin into the human body connecting the Internet of things (IoT) with the Internet of bio-nano things (IoBNT). We develop an experimental setup as a proof of concept and provide a detailed description of the testbed, its assembly and fabrication. Mathematical models for all components are derived and verified experimentally. Finally, we analyze the communications performance of the system and elaborate on future works.
在这项工作中,我们提出了一种新的热分子通信网关,允许通过人体皮肤进入人体,将物联网(IoT)与生物纳米物联网(IoBNT)连接起来。我们开发了一个实验装置作为概念验证,并提供了测试平台,其组装和制造的详细描述。推导了各部件的数学模型,并进行了实验验证。最后,对系统的通信性能进行了分析,并对今后的工作进行了阐述。
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引用次数: 0
CDM in Neural Communication Based on Oscillatory Characteristics of Membrane Potential 基于膜电位振荡特性的神经通讯CDM
IF 2.4 Q2 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-04-01 DOI: 10.1109/TMBMC.2025.3556841
Huiyu Luo;Yi Huang;Lin Lin
With the advancement of the Internet of Nanothings (IoNT), information networks within organisms are becoming increasingly sophisticated, making the transmission of data from IoNT to the external environment a key research focus. Neural communication, as a promising solution, utilizes action potentials (APs) to carry information. However, enhancing the efficiency of data transmission for multiple IoNT nodes in a complex biological environment presents significant challenges. To address these challenges, this paper proposes an adaptive code division multiplexing (CDM) schemes in neural communication based on the oscillatory characteristics of membrane potential, enabling parallel information transmission for multiple IoNT nodes. This scheme assigns each signal an orthogonal code sequence and superimposes them onto a shared channel. To accommodate the oscillatory properties described by the resonate-and-fire (RF) neuron model, our approach further encodes the superimposed signals in CDM schemes, converting both symbolic and numerical bits into binary data for transmission. Simulation results demonstrate that the proposed scheme significantly enhances interference resistance while enabling multiple signals to share a single neuron channel. This paper paves the way for the implementation of IoNT applications.
随着纳米物联网(Internet of Nanothings, IoNT)的发展,生物体内的信息网络变得越来越复杂,使得从纳米物联网到外部环境的数据传输成为一个重要的研究热点。神经通信利用动作电位(ap)传递信息,是一种很有前途的解决方案。然而,在复杂的生物环境中,提高多个IoNT节点的数据传输效率是一个重大挑战。为了解决这些问题,本文提出了一种基于膜电位振荡特性的神经通信自适应码分复用(CDM)方案,实现多个IoNT节点的并行信息传输。该方案为每个信号分配一个正交码序列,并将它们叠加到一个共享信道上。为了适应谐振-放电(RF)神经元模型所描述的振荡特性,我们的方法进一步编码CDM方案中的叠加信号,将符号和数字位转换为二进制数据进行传输。仿真结果表明,该方案在使多个信号共享一个神经元通道的同时,显著提高了抗干扰能力。本文为物联网应用的实现铺平了道路。
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引用次数: 0
The Role of Bioelectrical Patterns in Regulative Morphogenesis: An Evolutionary Simulation and Validation in Planarian Regeneration 生物电模式在调节形态发生中的作用:涡虫再生的进化模拟和验证
IF 2.3 Q2 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-03-30 DOI: 10.1109/TMBMC.2025.3575233
Sammy Hansali;Léo Pio-Lopez;Jennifer V. Lapalme;Michael Levin
Endogenous bioelectrical patterns are an important regulator of anatomical pattern during embryogenesis, regeneration, and cancer. While there are three known classes of instructive bioelectric patterns: directly encoding, indirectly encoding, and binary trigger, it is not known how these design principles could be exploited by evolution and what their relative advantages might be. To better understand the evolutionary role of bioelectricity in anatomical homeostasis, we developed a neural cellular automaton (NCA). We used evolutionary algorithms to optimize these models to achieve reliable morphogenetic patterns driven by the different ways in which tissues can interpret their bioelectrical pattern for downstream anatomical outcomes. We found that: (1) All three types of bioelectrical codes allow the reaching of target morphologies; (2) Resetting of the bioelectrical pattern and the change in duration of the binary trigger alter morphogenesis; (3) Direct pattern organisms show an emergent robustness to changes in initial anatomical configurations; (4) Indirect pattern organisms show an emergent robustness to bioelectrical perturbation; (5) Direct and indirect pattern organisms show a emergent generalizability competency to new (rotated) bioelectrical patterns; (6) Direct pattern organisms show an emergent repatterning competency in post-developmental-phase. Because our simulation was fundamentally a homeostatic system seeking to achieve specific goals in anatomical state space (the space of possible morphologies), we sought to determine how the system would react when we abrogated the incentive loop driving anatomical homeostasis. To abrogate the stress/reward system that drives error minimization, we used anxiolytic neuromodulators. Simulating the effects of selective serotonin reuptake inhibitors diminished the ability of artificial embryos to reduce error between anatomical state and bioelectric prepattern, leading to higher variance of developmental outcomes, global morphological degradation, and induced in some organisms a bistability with respect to possible anatomical outcomes. These computational findings were validated by data collected from in vivo experiments in SSRI exposure in planarian flatworm regeneration.
内源性生物电模式是胚胎发生、再生和癌变过程中解剖模式的重要调节因子。虽然有三种已知的指导性生物电模式:直接编码、间接编码和二进制触发,但尚不清楚这些设计原则如何被进化所利用,以及它们的相对优势是什么。为了更好地理解生物电在解剖稳态中的进化作用,我们开发了一个神经细胞自动机(NCA)。我们使用进化算法来优化这些模型,以获得可靠的形态发生模式,这些模式是由不同的组织方式驱动的,这些组织可以通过不同的方式来解释其生物电模式,从而获得下游解剖结果。我们发现:(1)所有三种类型的生物电编码都允许到达目标形态;(2)生物电模式的重置和二元触发持续时间的改变改变了形态发生;(3)直接模式生物对初始解剖结构的变化表现出紧急鲁棒性;(4)间接模式生物对生物电扰动表现出紧急鲁棒性;(5)直接模式和间接模式生物对新的(旋转的)生物电模式表现出一种新兴的一般化能力;(6)直接模式生物在发育后期表现出突发性的模式重组能力。由于我们的模拟基本上是一个寻求在解剖状态空间(可能的形态空间)中实现特定目标的稳态系统,因此我们试图确定当我们取消驱动解剖稳态的激励循环时系统将如何反应。为了消除导致错误最小化的压力/奖励系统,我们使用了抗焦虑神经调节剂。模拟选择性5 -羟色胺再摄取抑制剂的作用,降低了人工胚胎减少解剖状态和生物电预模式之间误差的能力,导致发育结果的更高差异,整体形态退化,并在某些生物体中诱导了可能解剖结果的双稳定性。这些计算结果通过在涡虫再生中暴露SSRI的体内实验收集的数据得到验证。
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IEEE Transactions on Molecular, Biological, and Multi-Scale Communications
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