A Biomechanical Model for Fluidization of Cells under Dynamic Strain

Abstract

Recent experiments have investigated the response of smooth muscle cells to transient stretch-compress (SC) and compress-stretch (CS) maneuvers. The results indicate that the transient SC maneuver causes a sudden fluidization of the cell while the CS maneuver does not. To understand this asymmetric behavior, we have built a biomechanical model to probe the response of stress fibers to the two maneuvers. The model couples the cross-bridge cycle of myosin motors with a viscoelastic Kelvin-Voigt element that represents the stress fiber. Simulation results point to the sensitivity of the myosin detachment rate to tension as the cause for the asymmetric response of the stress fiber to the CS and SC maneuvers. For the SC maneuver, the initial stretch increases the tension in the stress fiber and suppresses myosin detachment. The subsequent compression then causes a large proportion of the myosin population to disengage rapidly from actin filaments. This leads to the disassembly of the stress fibers and the observed fluidization. In contrast, the CS maneuver only produces a mild loss of myosin motors and no fluidization.

The impact of low-frequency, low-force cyclic stretching of human bronchi on airway responsiveness

“…In the case of a “stretch-compress” action (as in the present study), the muscle tension rises sharply at the start of the stimulus. This includes the response of the bronchial tree embedded within the elastic component of the bronchial structure [39]. …”

Microskeletal stiffness promotes aortic aneurysm by sustaining pathological vascular smooth muscle cell mechanosensation via Piezo1    

“…In light of our experimental findings, we developed a predictive biophysical kinetics model that incorporated three key actomyosin CSK events: CSK viscoelastic deformation and relaxation, actomyosin activation and contraction, and mechanical-induced Ca 2+ influx ( Figure 4a). We adopted the Kelvin-Voigt-Myosin (KVM) model 33 to specifically study how pathological increases of α-actinin2 in VSMC can lead to different mechanosensation dynamics ( Figure 4b) in AAA. In this model, Ca 2+ influx causes myosin activation and sliding leading to deformed CSK which is relies on viscoelasitic properties regulated by α-actinin2 crosslinking.…”

“…In the KVM model, the Kelvin-Voigt element, which is the cell CSK is modelled as a viscoelastic material consisting of elastic stress fiber (SF) with an elastic module of KSF and a viscous component with viscosity of η. The contractile myosin (CM) element is modelled in series configuration with the viscoelastic CSK structure 33,59 . The elastic module of KSF is proportional to the amount of α-actinin2 and is described as , where…”

Cellular mechanosensing of the biophysical microenvironment: A review of mathematical models of biophysical regulation of cell responses

“…, the cell fluidization (cytoskeletal disassembly) mechanism [86, 87], mechanochemical molecules such as activation of the Rho pathway [88], and inhomogeneous SFs contraction [97]. Recently, Wu et al proposed a Kelvin-Voight-myosin (KVM) model, which couples assembly-disassembly of myosin motors with a single viscoelastic Kelvin-Voigt stress fiber [98]. Their model predicts that tension-regulated myosin detachment is the main reason for cell fluidization in response to transient loading.…”