The Direction of Cyclic Stretch-Induced Cell and Stress Fiber Alignment Depends on Matrix Rigidity
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We have previously reported that stress fibers (SFs) in cells with normal contractility reorient perpendicular to the direction of cyclic stretch [1], while cells treated with inhibitors of myosin light-chain kinase (MLCK) or members of the Rho GTPase pathway oriented parallel to the direction of stretch [1, 2]. Our theoretical modeling predicts that myosin II acts as a tension sensor acting to maintain SF tension through sliding along actin filaments under low strain rates or promoting SF reorientation under high strain rates [3]. This model predicts that SFs on stiff elastic substrates are at an optimal level of tension and that cyclic stretching subjects these SFs to excessive loads in the direction of stretch, hence SFs preferentially orient away from the direction of stretch. On soft substrate, intracellular tension is expected to be much lower than on stiff substrates [4]. Consequently, we postulated that stretching cells on a soft substrate would induce cell and SF alignment parallel to the direction of stretch in a manner dependent on cell contractility.
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