The Mechanosensing Systems Of Cells

How do cellular structures, including stress fibers and focal adhesions, of cell’s mechanosensing system interplay with each another through their molecular-level properties/behaviors to sense and response to the macroscopic extracellular mechanical properties, and modulate their collective behaviors? This is an important research topic that has attracted great attention from many researchers. However, an integrated modeling of cell’s mechanosensing system is still lacking. As an important part of this mechanosensing system, focal adhesions, which directly link the cells to the extracellular matrix or other cells, have been well studied in the past decades. Especially the effects of homogeneous and isotropic substrates of different stiffness, shape and other mechanical properties in cell-matrix system have been intensively studied. In this thesis, we will focus on natural and artificial substrates with some sophisticated mechanical properties, such as modulus gradation, anisotropy and elastomers regulated by pre-stretch, to explore their effects on the behaviors of cell-matrix adhesion. Our theoretical and numerical results show that these mechanical designs in natural and artificial materials can provide an effective strategy to modulate the performance and stability of cell adhesion, as well as the fictional response when sliding occurs at the interface. Our results imply the opportunity that tissues or intracellular structures with similar material properties might be used to control adhesion-mediated behaviors of cells. In the other part of this thesis, an integrated model of cell’s mechanosensing system is established by considering the stochastic dynamics that couples various aspects of the system, including motor contraction, assembly and disassembly of both stress fibers and focal adhesions, the multi-layer hierarchy of focal adhesion, the catch bond behavior of integrin-based adhesion and talin-vinculin complex, etc. We use this integrated model of cell’s mechanosensing system to investigate the time-varying behaviors of stress fiber and focal adhesion, in response to various geometric and mechanical cues including rigidity, curvature and cyclic stretch. By doing this, we reveal multiple mechanisms that are consistent to some key experimental phenomena on the topic. For example, the complex of focal adhesions and stress fibers will grow from a length shorter than 1 micrometer to dozens of micrometers; suppressing and recovering the activity of myosins lead to disassembly and reassembly of stress fibers and focal adhesions, respectively; cells of micrometerscale have the ability to sense the shape with curvature radius of several millimeters; the stress level within focal adhesions is homostatic; externally applied loading will promote the formation of focal adhesions, etc. This model of cell’s mechanosensing system integrates the mechanical and stochastic behaviors of subcellular structures from multiple scales, and can serve as a general framework in studying the dynamic cellular behaviors in response to mechanical stimuli.