Two Characteristic Regimes in Frequency-Dependent Dynamic Reorientation of Fibroblasts on Cyclically Stretched Substrates

Abstract

Cells adherent on a cyclically stretched substrate with a periodically varying uniaxial strain are known to dynamically reorient nearly perpendicular to the strain direction. We investigate the dynamic reorientation of rat embryonic and human fibroblast cells over a range of stretching frequency from 0.0001 to 20 s(-1) and strain amplitude from 1% to 15%. We report quantitative measurements that show that the mean cell orientation changes exponentially with a frequency-dependent characteristic time from 1 to 5 h. At subconfluent cell densities, this characteristic time for reorientation shows two characteristic regimes as a function of frequency. For frequencies below 1 s(-1), the characteristic time decreases with a power law as the frequency increases. For frequencies above 1 s(-1), it saturates at a constant value. In addition, a minimum threshold frequency is found below that no significant cell reorientation occurs. Our results are consistent for the two different fibroblast types and indicate a saturation of molecular mechanisms of mechanotransduction or response machinery for subconfluent cells within the frequency regime under investigation. For confluent cell layers, we observe similar behaviors of reorientation under cyclic stretch but no saturation in the characteristic time with frequency, suggesting that cell-cell contacts can play an important role in the response machinery of cells under mechanical strain.

A thermodynamically motivated model for stress-fiber reorganization

“…Effect of strain amplitude The studies of Kaunas et al (2005) and Jungbauer et al (2008) have demonstrated that the propensity of stress-fibers to align perpendicular to the loading direction increases with increasing applied strain-rate for a triangular imposed strain waveform. For example, as seen above with a strain amplitude of 0.1, the stress-fibers align perpendicular to the imposed loading direction when the cyclic frequency = 1 Hz but the stress-fiber distribution is approximately isotropic when = 0.1 Hz.…”

Biomimetic study of rolling transport through smooth muscle contraction

“…Cells are known to respond to mechanical forces exerted through surrounding fluid, adhering beads or substrates [9,[12][13][14], and they could detach, slip or roll on a substrate in response to these forces [15][16][17][18][19][20][21][22]. For example, cells on a cyclically stretched substrate tend to reorient themselves away from the stretching direction [23][24][25][26][27], and cells migrate along a substrate with rigidity gradient (durotaxis) [18]. Blood cells are found to undergo a transition from rolling to translational motion on a blood vessel wall under increasing hydrodynamic shear forces [19], exemplifying a general fact that it takes less effort for a round object to roll than to slip on a substrate [28,29].…”

The Number of Cyclic Stretch Regulates Cellular Elasticity in C2C12 Myoblasts

“…A variety of mechanical stimuli have the potential to regulate cellular physiology. With respect to cyclic stretch, changing the magnitude or frequency rearranges cell orientation [8,18] and cytoskeletal networks [19], and upor down-regulates cell growth rate and protein synthesis [20]. Moreover, application of a large number (~1000) of cyclic stretches also affects cell growth [21] and cell orientation.…”