Chowdhury Farhan, Na Sungsoo, Collin Olivier, Tay Bernard, Li Fang, Tanaka Testuya, Leckband Deborah E, Wang Ning
Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Biophys J. 2008 Dec 15;95(12):5719-27. doi: 10.1529/biophysj.108.139832. Epub 2008 Oct 3.
A living cell deforms or flows in response to mechanical stresses. A recent report shows that dynamic mechanics of living cells depends on the timescale of mechanical loading, in contrast to the prevailing view of some authors that cell rheology is timescale-free. Yet the molecular basis that governs this timescale-dependent behavior is elusive. Using molecular dynamics simulations of protein-protein noncovalent interactions, we show that multipower laws originate from a nonequilibrium-to-equilibrium transition: when the loading rate is faster than the transition rate, the power-law exponent alpha(1) is weak; when the loading rate is slower than the transition rate, the exponent alpha(2) is strong. The model predictions are confirmed in both embryonic stem cells and differentiated cells. Embryonic stem cells are less stiff, more fluidlike, and exhibit greater alpha(1) than their differentiated counterparts. By introducing a near-equilibrium frequency f(eq), we show that all data collapse into two power laws separated by f/f(eq), which is unity. These findings suggest that the timescale-dependent rheology in living cells originates from the nonequilibrium-to-equilibrium transition of the dynamic response of distinct, force-driven molecular processes.
活细胞会因机械应力而发生变形或流动。最近的一份报告表明，活细胞的动态力学取决于机械加载的时间尺度，这与一些作者的普遍观点相反，即细胞流变学与时间尺度无关。然而，支配这种时间尺度依赖性行为的分子基础尚不清楚。通过蛋白质 - 蛋白质非共价相互作用的分子动力学模拟，我们表明多幂律源自非平衡到平衡的转变：当加载速率快于转变速率时，幂律指数α(1)较弱；当加载速率慢于转变速率时，指数α(2)较强。该模型预测在胚胎干细胞和分化细胞中均得到证实。胚胎干细胞比其分化后的对应细胞更柔软、更具流体特性，并且表现出更大的α(1)。通过引入近平衡频率f(eq)，我们表明所有数据都汇聚为两个由f/f(eq)分隔的幂律，其中f/f(eq)等于1。这些发现表明，活细胞中时间尺度依赖性流变学源于不同的、力驱动的分子过程的动态响应的非平衡到平衡转变。
