Abstract
Cells modulate themselves in response to the surrounding environment like substrate elasticity, exhibiting structural reorganization driven by the contractility of cytoskeleton. The cytoskeleton is the scaffolding structure of eukaryotic cells, playing a central role in many mechanical and biological functions. It is composed of a network of actins, actin cross-linking proteins (ACPs), and molecular motors. The motors generate contractile forces by sliding couples of actin filaments in a polar fashion, and the contractile response of the cytoskeleton network is known to be modulated also by external stimuli, such as substrate stiffness. This implies an important role of actomyosin contractility in the cell mechano-sensing. However, how cells sense matrix stiffness via the contractility remains an open question. Here, we present a 3-D Brownian dynamics computational model of a cross-linked actin network including the dynamics of molecular motors and ACPs. The mechano-sensing properties of this active network are investigated by evaluating contraction and stress in response to different substrate stiffness. Results demonstrate two mechanisms that act to limit internal stress: (i) In stiff substrates, motors walk until they exert their maximum force, leading to a plateau stress that is independent of substrate stiffness, whereas (ii) in soft substrates, motors walk until they become blocked by other motors or ACPs, leading to submaximal stress levels. Therefore, this study provides new insights into the role of molecular motors in the contraction and rigidity sensing of cells.
Highlights
Cells modulate their properties and activities in response to the surrounding environment, via morphological rearrangements driven by cytoskeletal contractility and reorganization
We investigate the role of molecular motors as rigidity sensors and predict the contractile stress and strain of actomyosin networks tethered to 3-D cubical domains
Despite the oversimplifications and assumptions made in the described system which only includes the dynamics of motors and actin cross-linking proteins (ACPs), the simulated actin network exhibits macroscopic contractile behaviors remarkably similar to several experiments [12,27,28], further indicating that microscopic properties of individual constituents govern the network responses, and that motors play a central role in mechano-sensing
Summary
Cells modulate their properties and activities in response to the surrounding environment, via morphological rearrangements driven by cytoskeletal contractility and reorganization. Cells generate low forces with randomly aligned actin filaments, leading to a weak response with wrinkles or strains of the substrates. Other experimental results collectively suggested that on stiff substrates, cells tend to deform intracellular structures rather than the substrate as seen in myosin/actin striations [5,6,7,8]. Several mechanisms governing such mechano-sensing of cells have been proposed in experimental studies, and multiple mechanisms likely exist involving different intracellular structures. Non-muscle myosins were shown to be crucial for stem cells to sense matrix elasticity [15]. Local forces acting on both integrin-mediated [16,17] and cadherin-mediated adhesions exhibit a similar relationship with stiffness [18,19]
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