It is known that mechanical forces play critical roles in physiology and diseases but the underlying mechanisms remain largely unknown[1].Most studies on the role of forces focus on cell surface molecules and cytoplas...It is known that mechanical forces play critical roles in physiology and diseases but the underlying mechanisms remain largely unknown[1].Most studies on the role of forces focus on cell surface molecules and cytoplasmic proteins.However,increasing evidence suggests that nuclear mechanotransduction impacts nuclear activities and functions.Recently we have revealed that transgene dihydrofolate reductase(DHFR)gene expression is directly upregulated via cell surface forceinduced stretching of chromatin [2].Here we show that endogenous genes are also upregulated directly by force via integrins.We present evidence on an underlying mechanism of how gene transcription is regulated by force.We have developed a technique of elastic round microgels to quantify 3D tractions in vitro and in vivo[3].We report a synthetic small molecule(which has been stiffened structurally)that inhibits malignant tumor repopulating cell growth in a low-stiffness(force)microenvironment and cancer metastasis in mouse models without detectable toxicity[4].These findings suggest that direct nuclear mechanotransduction impacts mechanobiology and mechanomedicine at cellular and molecular levels.展开更多
Cellular behaviors such as migration,spreading,and differentiation arise from the interplay of cell–matrix interactions.The comprehension of this interplay has been advanced by the motor-clutch model,a theoretical fr...Cellular behaviors such as migration,spreading,and differentiation arise from the interplay of cell–matrix interactions.The comprehension of this interplay has been advanced by the motor-clutch model,a theoretical framework that captures the binding-unbinding kinetics of mechanosensitive membrane-bound proteins involved in mechanochemical signaling,such as integrins.Since its introduction and subsequent development as a computational tool,the motor clutch model has been instrumental in elucidating the impact of biophysical factors on cellular mechanobiology.This review aims to provide a comprehensive overview of recent advances in the motor-clutch modeling framework,its role in elucidating the relationships between mechanical forces and cellular processes,and its potential applications in mechanomedicine.展开更多
基金supported by funds from National Institutes of Health,USA and Huazhong University of Science and Technology,Wuhan,Chinathe support from Hoeft Professorship at University of Illinois at Urbana-Champaign
文摘It is known that mechanical forces play critical roles in physiology and diseases but the underlying mechanisms remain largely unknown[1].Most studies on the role of forces focus on cell surface molecules and cytoplasmic proteins.However,increasing evidence suggests that nuclear mechanotransduction impacts nuclear activities and functions.Recently we have revealed that transgene dihydrofolate reductase(DHFR)gene expression is directly upregulated via cell surface forceinduced stretching of chromatin [2].Here we show that endogenous genes are also upregulated directly by force via integrins.We present evidence on an underlying mechanism of how gene transcription is regulated by force.We have developed a technique of elastic round microgels to quantify 3D tractions in vitro and in vivo[3].We report a synthetic small molecule(which has been stiffened structurally)that inhibits malignant tumor repopulating cell growth in a low-stiffness(force)microenvironment and cancer metastasis in mouse models without detectable toxicity[4].These findings suggest that direct nuclear mechanotransduction impacts mechanobiology and mechanomedicine at cellular and molecular levels.
文摘Cellular behaviors such as migration,spreading,and differentiation arise from the interplay of cell–matrix interactions.The comprehension of this interplay has been advanced by the motor-clutch model,a theoretical framework that captures the binding-unbinding kinetics of mechanosensitive membrane-bound proteins involved in mechanochemical signaling,such as integrins.Since its introduction and subsequent development as a computational tool,the motor clutch model has been instrumental in elucidating the impact of biophysical factors on cellular mechanobiology.This review aims to provide a comprehensive overview of recent advances in the motor-clutch modeling framework,its role in elucidating the relationships between mechanical forces and cellular processes,and its potential applications in mechanomedicine.
