{"title":"Role of NFAT5 in Hypertonic Stress-Induced Atherosclerosis in Endothelium","authors":"P. Ma, Wanqian Liu, Li Yang","doi":"10.32604/mcb.2019.07363","DOIUrl":"https://doi.org/10.32604/mcb.2019.07363","url":null,"abstract":"","PeriodicalId":48719,"journal":{"name":"Molecular & Cellular Biomechanics","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87408121","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}
Lucy Wanjiru Njunge, Andreanne Poppy Estania, Li Yang
{"title":"hnRNPK a Possible Mechanosensitive Gene: Its Function in Chondrocytes and Osteoarthritis","authors":"Lucy Wanjiru Njunge, Andreanne Poppy Estania, Li Yang","doi":"10.32604/mcb.2019.07116","DOIUrl":"https://doi.org/10.32604/mcb.2019.07116","url":null,"abstract":"","PeriodicalId":48719,"journal":{"name":"Molecular & Cellular Biomechanics","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87421381","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}
{"title":"From Biomechanics to Molecular Affinity to Systems Immunology – My Path in Biomedical Engineering That is Inspired by Dr. YC Fung","authors":"N. Jiang","doi":"10.32604/mcb.2019.07486","DOIUrl":"https://doi.org/10.32604/mcb.2019.07486","url":null,"abstract":"","PeriodicalId":48719,"journal":{"name":"Molecular & Cellular Biomechanics","volume":"357 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86799085","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}
Tractions exerted by cells on the extracellular matrix (ECM) are critical in many important physiological and pathological processes such as embryonic morphogenesis, cell migration, wound healing, and cancer metastasis. Traction Force Microscopy (TFM) is a robust tool to quantify cellular tractions during cell-matrix interactions. It works by measuring the motion of fiducial markers inside the ECM in response to cellular tractions and using this information to infer the traction field. Most applications of this technique have heretofore assumed that the ECM is homogeneous and isotropic [1], although the native ECM is typically composed of fibrous networks, and thus heterogeneous and anisotropic. In this work, we present a novel nonlinear TFM approach to recover 3D tractions exerted by cells fully encapsulated in fibrous hydrogels that mimic the in-vivo cellular environment. We pose the problem as an inverse hyperelasticity problem, with the objective of determining the traction field that is consistent with the measured displacement field in the ECM. We formulate the inverse problem as a constrained minimization problem and develop an efficient adjoint-based minimization technique to solve it [2]. In particular, we account for the fibrous character of the ECM by employing a microstructure-based homogenization model that links the microscopic features of the fibrous gels to the macroscopic response. We apply our TFM approach to in-silico problems with realistic geometric models of NIH 3T3 and microglial cells. We find that the proposed algorithm is able to accurately recover the traction fields. By comparison with results obtained using isotropic models (e.g., Neo-Hookean model and Blatz model), we find that the error introduced by neglecting the fibrous nature of the ECM is significant. These results suggest that it is crucial to account for the microstructure of the ECM to accurately quantify cellular forces in physiologically relevant settings. In light of this, our algorithm represents a step toward more accurate, broadly-applicable 3D TFM.
{"title":"Recovery of 3D Tractions Exerted by Cells on Fibrous Extracellular Matrices","authors":"Dawei Song, Nicholas R Hugenberg, A. Oberai","doi":"10.32604/mcb.2019.07138","DOIUrl":"https://doi.org/10.32604/mcb.2019.07138","url":null,"abstract":"Tractions exerted by cells on the extracellular matrix (ECM) are critical in many important physiological and pathological processes such as embryonic morphogenesis, cell migration, wound healing, and cancer metastasis. Traction Force Microscopy (TFM) is a robust tool to quantify cellular tractions during cell-matrix interactions. It works by measuring the motion of fiducial markers inside the ECM in response to cellular tractions and using this information to infer the traction field. Most applications of this technique have heretofore assumed that the ECM is homogeneous and isotropic [1], although the native ECM is typically composed of fibrous networks, and thus heterogeneous and anisotropic. In this work, we present a novel nonlinear TFM approach to recover 3D tractions exerted by cells fully encapsulated in fibrous hydrogels that mimic the in-vivo cellular environment. We pose the problem as an inverse hyperelasticity problem, with the objective of determining the traction field that is consistent with the measured displacement field in the ECM. We formulate the inverse problem as a constrained minimization problem and develop an efficient adjoint-based minimization technique to solve it [2]. In particular, we account for the fibrous character of the ECM by employing a microstructure-based homogenization model that links the microscopic features of the fibrous gels to the macroscopic response. We apply our TFM approach to in-silico problems with realistic geometric models of NIH 3T3 and microglial cells. We find that the proposed algorithm is able to accurately recover the traction fields. By comparison with results obtained using isotropic models (e.g., Neo-Hookean model and Blatz model), we find that the error introduced by neglecting the fibrous nature of the ECM is significant. These results suggest that it is crucial to account for the microstructure of the ECM to accurately quantify cellular forces in physiologically relevant settings. In light of this, our algorithm represents a step toward more accurate, broadly-applicable 3D TFM.","PeriodicalId":48719,"journal":{"name":"Molecular & Cellular Biomechanics","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89594684","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}
Professor Y.C. Fung has made tremendous impacts on science, engineering and humanity through his research and its applications, by setting the highest standards, through educating many students and their students, and providing his exemplary leadership. He has applied his profound knowledge and elegant analytical methods to the study of biomedical problems with rigor and excellence. He established the foundations of biomechanics in living tissues and organs. Through his vision of the power of “making models” to explain and predict biological phenomena, Dr. Fung opened up new vista for bioengineering, from organs-systems to molecules-genes, and has provided the foundation of research activities in many institutions in the United States and the world. He has made outstanding contributions to education in bioengineering, service to professional organizations, and translation to industry and clinical medicine. He is widely recognized as the Father of Biomechanics and the leading Bioengineer in the world. His extraordinary achievements and commands in science, engineering and the arts make him a Renaissance Man for the world.
{"title":"Warmest Congratulations to Dr. Yuan-Cheng Fung at His Centennial Celebration","authors":"S. Chien","doi":"10.32604/mcb.2019.07689","DOIUrl":"https://doi.org/10.32604/mcb.2019.07689","url":null,"abstract":"Professor Y.C. Fung has made tremendous impacts on science, engineering and humanity through his research and its applications, by setting the highest standards, through educating many students and their students, and providing his exemplary leadership. He has applied his profound knowledge and elegant analytical methods to the study of biomedical problems with rigor and excellence. He established the foundations of biomechanics in living tissues and organs. Through his vision of the power of “making models” to explain and predict biological phenomena, Dr. Fung opened up new vista for bioengineering, from organs-systems to molecules-genes, and has provided the foundation of research activities in many institutions in the United States and the world. He has made outstanding contributions to education in bioengineering, service to professional organizations, and translation to industry and clinical medicine. He is widely recognized as the Father of Biomechanics and the leading Bioengineer in the world. His extraordinary achievements and commands in science, engineering and the arts make him a Renaissance Man for the world.","PeriodicalId":48719,"journal":{"name":"Molecular & Cellular Biomechanics","volume":"155 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78000480","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}
{"title":"A New Mass Effect Research Rat Model to Explore the Occuping Effect on Secondary Brain Injuries after ICH","authors":"Yuhua Gong, Shilei Hao, Bochu Wang","doi":"10.32604/mcb.2019.07095","DOIUrl":"https://doi.org/10.32604/mcb.2019.07095","url":null,"abstract":"","PeriodicalId":48719,"journal":{"name":"Molecular & Cellular Biomechanics","volume":"302 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74964242","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}
{"title":"The Role of Shear Stress in Atherosclerotic Plaque Progression, Destabilization and Rupture","authors":"J. J. Wentzel","doi":"10.32604/mcb.2019.05696","DOIUrl":"https://doi.org/10.32604/mcb.2019.05696","url":null,"abstract":"","PeriodicalId":48719,"journal":{"name":"Molecular & Cellular Biomechanics","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79864824","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}
Yang Wang, S. Ge, Junyang Huang, Ruolin Du, T. Yin, Guixue Wang, Yazhou Wang
: Zonula occludens-1 (ZO-1) is a peripheral membrane protein belongs to the family of zona occludens proteins and plays an important role as a scaffold protein which cross-links and anchors tight junction (TJ) strand proteins, within the lipid bilayer, to the actin cytoskeleton [1-2] . Stent implantation is the most effective method in the treatment of cardiovascular disease which always destroy junctions of endothelial cells, the functions of the tight junction were also affected. However, the role of ZO-1 before and after stent implantation has not been fully understood. In this study, the expression of ZO-1 were analyzed by qPCR, western blot and immunofluorescence in vivo and in vitro . In vivo experiments were developed in two animal modes, carotid ligation of ApoE -/- mice for 48 h and abdominal aorta poly (L-lactic acid) stents implantation of male SD rats for indicated time (1 week, 1 month, 3 month and 1 year). In vitro, HUVECs were exposed to fluid shear stress and static pressure respectively. Namely, shear stress at 5 dyn/cm 2 (low shear stress, LSS) and 12 dyn/cm 2 (high shear stress) for 6 h, and 40 kPa static pressure for 6 h and 12 h. In vivo , expression of ZO-1 showed interestingly lower, compared to control in ApoE -/-mice and SD rats, except stents implantation at 3 month. In vitro , the expression level of ZO-1 showed higher at indicated shear stress, no statistical difference under static pressure at 6 h but significantly higher at 12 h, compared to control. Fluorescent staining showed more loose connection between cells and surrounding edges of the cells presented a gear shape with many small forks. In conclusion, we tried to indicate the role of ZO-1 before and after stent implantation by applying different mechanical stimulations respectively to imitate the mechanical environment endothelial cells might confront in vivo . Interestingly, we found that expression of ZO-1 was diametrically opposed in vitro and in vivo except stents implantation for 3 month in rats. Overall, our research revealed that ZO-1 response to multiple-mechanical stimulations, and ZO-1 might be inhibited or degraded in RNA level for multiplex mechanical stimulations in vivo , which shall pave the way for further research.
{"title":"Endothelial Tight Junction Protein ZO-1 Response to Multiple-Mechanical Stimulations After Stent Implamtation","authors":"Yang Wang, S. Ge, Junyang Huang, Ruolin Du, T. Yin, Guixue Wang, Yazhou Wang","doi":"10.32604/mcb.2019.07300","DOIUrl":"https://doi.org/10.32604/mcb.2019.07300","url":null,"abstract":": Zonula occludens-1 (ZO-1) is a peripheral membrane protein belongs to the family of zona occludens proteins and plays an important role as a scaffold protein which cross-links and anchors tight junction (TJ) strand proteins, within the lipid bilayer, to the actin cytoskeleton [1-2] . Stent implantation is the most effective method in the treatment of cardiovascular disease which always destroy junctions of endothelial cells, the functions of the tight junction were also affected. However, the role of ZO-1 before and after stent implantation has not been fully understood. In this study, the expression of ZO-1 were analyzed by qPCR, western blot and immunofluorescence in vivo and in vitro . In vivo experiments were developed in two animal modes, carotid ligation of ApoE -/- mice for 48 h and abdominal aorta poly (L-lactic acid) stents implantation of male SD rats for indicated time (1 week, 1 month, 3 month and 1 year). In vitro, HUVECs were exposed to fluid shear stress and static pressure respectively. Namely, shear stress at 5 dyn/cm 2 (low shear stress, LSS) and 12 dyn/cm 2 (high shear stress) for 6 h, and 40 kPa static pressure for 6 h and 12 h. In vivo , expression of ZO-1 showed interestingly lower, compared to control in ApoE -/-mice and SD rats, except stents implantation at 3 month. In vitro , the expression level of ZO-1 showed higher at indicated shear stress, no statistical difference under static pressure at 6 h but significantly higher at 12 h, compared to control. Fluorescent staining showed more loose connection between cells and surrounding edges of the cells presented a gear shape with many small forks. In conclusion, we tried to indicate the role of ZO-1 before and after stent implantation by applying different mechanical stimulations respectively to imitate the mechanical environment endothelial cells might confront in vivo . Interestingly, we found that expression of ZO-1 was diametrically opposed in vitro and in vivo except stents implantation for 3 month in rats. Overall, our research revealed that ZO-1 response to multiple-mechanical stimulations, and ZO-1 might be inhibited or degraded in RNA level for multiplex mechanical stimulations in vivo , which shall pave the way for further research.","PeriodicalId":48719,"journal":{"name":"Molecular & Cellular Biomechanics","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82511922","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}
Danyang Yue, Yijuan Fan, Juan Lu, Mengxue Zhang, Jin Zhou, Yuying Bai, Jun Pan
: Mesenchymal Stem Cells (MSCs) are recruited to the musculoskeletal system following trauma [1] or chemicals stimulation [2]. The regulation of their differentiation into either bone or cartilage cells is a key question. The fluid shear stress (FSS) is of pivotal importance to the development, function and even the repair of all tissues in the musculoskeletal system [3]. We previously found that MSCs are sensitive enough to distinguish a slight change of FSS stimulation during their differentiation commitment to bone or cartilage cells, and the internal mechanisms. In detail, MSCs were exposed to laminar FSS linearly increased from 0 to 10 dyn/cm 2 in 0, 2, or 20 min and maintained at 10 dyn/cm 2 for a total of 20 min (termed as ΔSS of 0-0', 0-2', and 0-20', respectively, representing more physiological (0-0') and non-physiological (0-2' and 0-20') ΔSS treatments). 0-0' facilitated MSC differentiation towards chondrogenic but not osteogenic phenotype. In contrast, 0-2' promoted MSCs towards osteogenic but not chondrogenic phenotype. 0-20' elicited the modest osteogenic and chondrogenic phenotypes [4]. In addition, we disclosed that 20 min of ΔSS could compete with 5 days' chemical and 2 days' substrate stiffness inductions, demonstrating ΔSS is potent regulator for MSC differentiation control [5]. We found that the ΔSS induced MSC differentiation into osteogenic or chondrogenic cells is directed through the modulation of cation-selective channels (MSCCs), intracellular calcium levels and F-actin. Here we demonstrate that the 0-2' induced significant lamin A; the 0-0' induced similar lamin A to 0-2' and 0-20' elicited less lamin A. A special ΔSS of 0-1' is found to induce osteogenic differentiation comparable to 0-2' and chondrogenic differentiation comparable to 0-0' as well as the most lamin A. Lamin A has no influence on the expression of runx2, a key transcription factor in osteogenic differentiation, but has affected the expression of sox9, a key transcription factor in chondrogenic differentiation. Our study presents evidences that the MSCs are highly sensitive to discriminate different ΔSS loads and differentiate towards the osteogenic or chondrogenic phenotype by regulating MSCCs and the subsequent [Ca 2+ ] i increase, F-actin assembly and Lamin A expression, which provides guidance for training osteoporosis and osteoarthritis patients and stresses the possible application in MSCs linage specification.
{"title":"The Rate of Fluid Shear Stress is a Potent Regulator for Lineage Commitment of Mesenchymal Stem Cells Through Modulating [Ca2+]i, F-actin and Lamin A","authors":"Danyang Yue, Yijuan Fan, Juan Lu, Mengxue Zhang, Jin Zhou, Yuying Bai, Jun Pan","doi":"10.32604/mcb.2019.07084","DOIUrl":"https://doi.org/10.32604/mcb.2019.07084","url":null,"abstract":": Mesenchymal Stem Cells (MSCs) are recruited to the musculoskeletal system following trauma [1] or chemicals stimulation [2]. The regulation of their differentiation into either bone or cartilage cells is a key question. The fluid shear stress (FSS) is of pivotal importance to the development, function and even the repair of all tissues in the musculoskeletal system [3]. We previously found that MSCs are sensitive enough to distinguish a slight change of FSS stimulation during their differentiation commitment to bone or cartilage cells, and the internal mechanisms. In detail, MSCs were exposed to laminar FSS linearly increased from 0 to 10 dyn/cm 2 in 0, 2, or 20 min and maintained at 10 dyn/cm 2 for a total of 20 min (termed as ΔSS of 0-0', 0-2', and 0-20', respectively, representing more physiological (0-0') and non-physiological (0-2' and 0-20') ΔSS treatments). 0-0' facilitated MSC differentiation towards chondrogenic but not osteogenic phenotype. In contrast, 0-2' promoted MSCs towards osteogenic but not chondrogenic phenotype. 0-20' elicited the modest osteogenic and chondrogenic phenotypes [4]. In addition, we disclosed that 20 min of ΔSS could compete with 5 days' chemical and 2 days' substrate stiffness inductions, demonstrating ΔSS is potent regulator for MSC differentiation control [5]. We found that the ΔSS induced MSC differentiation into osteogenic or chondrogenic cells is directed through the modulation of cation-selective channels (MSCCs), intracellular calcium levels and F-actin. Here we demonstrate that the 0-2' induced significant lamin A; the 0-0' induced similar lamin A to 0-2' and 0-20' elicited less lamin A. A special ΔSS of 0-1' is found to induce osteogenic differentiation comparable to 0-2' and chondrogenic differentiation comparable to 0-0' as well as the most lamin A. Lamin A has no influence on the expression of runx2, a key transcription factor in osteogenic differentiation, but has affected the expression of sox9, a key transcription factor in chondrogenic differentiation. Our study presents evidences that the MSCs are highly sensitive to discriminate different ΔSS loads and differentiate towards the osteogenic or chondrogenic phenotype by regulating MSCCs and the subsequent [Ca 2+ ] i increase, F-actin assembly and Lamin A expression, which provides guidance for training osteoporosis and osteoarthritis patients and stresses the possible application in MSCs linage specification.","PeriodicalId":48719,"journal":{"name":"Molecular & Cellular Biomechanics","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90521271","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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