Abstract
When plated onto substrates, cell morphology and even stem-cell differentiation are influenced by the stiffness of their environment. Stiffer substrates give strongly spread (eventually polarized) cells with strong focal adhesions and stress fibers; very soft substrates give a less developed cytoskeleton and much lower cell spreading. The kinetics of this process of cell spreading is studied extensively, and important universal relationships are established on how the cell area grows with time. Here, we study the population dynamics of spreading cells, investigating the characteristic processes involved in the cell response to the substrate. We show that unlike the individual cell morphology, this population dynamics does not depend on the substrate stiffness. Instead, a strong activation temperature dependence is observed. Different cell lines on different substrates all have long-time statistics controlled by the thermal activation over a single energy barrier ΔG ≈ 18 kcal/mol, whereas the early-time kinetics follows a power law ∼t5. This implies that the rate of spreading depends on an internal process of adhesion complex assembly and activation; the operational complex must have five component proteins, and the last process in the sequence (which we believe is the activation of focal adhesion kinase) is controlled by the binding energy ΔG.
Highlights
Matrix stiffness is known to affect cell size and morphology [1,2,3]
The time we measure is the sum of the adhesion lag time and the time to reach our binary criterion for the start of spreading
The distribution in our data is due to the statistical distribution of the ‘‘lag times.’’ Our results show that the stochasticity of lag time has structure
Summary
Matrix stiffness is known to affect cell size and morphology [1,2,3]. When cells are plated onto soft substrates, their footprint will not increase as much as on stiff substrates, and their spreading will be more isotropic; the resulting cells will be round and dome-like in shape. The same cells will spread very strongly, develop concentrated focal adhesion clusters and stress fibers of bundled F-actin, and eventually polarize to initiate migration. This leads to several well-documented biological functions in tissues: variable stem-cell differentiation pathways [1,4], the fibroblast-myofibroblast transition near scar tissue [5,6,7], fibrosis in smooth-muscle cells near rigid plaque or scar tissue [8,9], and the stiffer nature of tumor cells [10,11]. After polarization is triggered on stiff substrates, the cell may start moving in a particular direction
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