Chen Yang, Wang Lei, Huang Hao, Tan Ruizhe, Zhao Jupeng, Yang Shenyu, Zeng Rong, Wu Hao, Zhang Jiaqing, Yu Bin, Tu Mei
Department of Materials Science and Engineering, PR China; Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Jinan University, Guangzhou 510632, PR China.
Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
J Mech Behav Biomed Mater. 2016 Apr;57:42-54. doi: 10.1016/j.jmbbm.2015.11.005. Epub 2015 Nov 23.
The extent of substrate stiffness has been shown to be predominant in regulating cellular behaviors. Previous studies have used matrices such as elastomers or hydrogels to understand cell behavior. Herein, liquid crystalline matrices that resemble movable morphology of biomembrane and viscoelasticity were fabricated with tunable storage modulus for the evaluation of the modulus-driven cell behaviors. Our results demonstrated that NIH/3T3 cells showed a hypersensitive response to the storage modulus of liquid crystalline substrates by the alteration in attachment, spreading, proliferation and viability, polarization, cell cycle and apoptosis, and activity of mechano-transduction-related signal molecules including FAK, paxillin and ERK. The octyl hydroxypropyl cellulose substrates (OPC-1-5) with intermediate storage modulus of 12,312Pa and 7228Pa (OPC-2 and OPC-3 respectively) could provide more beneficial adhesion conditions leading to a larger spreading area, more elongated morphology and higher proliferation rates possibly through paxillin-ERK pathway, whereas the substrates with the highest or lowest storage modulus (16,723Pa, OPC-1; and 41Pa, OPC-5, respectively) appeared unfavorable for cell growth. Our study provides insights into the mechanism of modulus-driven cellular behaviors for better design of bioengineered cell substrates.
已证明底物刚度在调节细胞行为方面起主要作用。先前的研究使用了诸如弹性体或水凝胶等基质来了解细胞行为。在此,制备了具有类似于生物膜可移动形态和粘弹性的液晶基质,其储能模量可调,用于评估模量驱动的细胞行为。我们的结果表明,NIH/3T3细胞通过附着、铺展、增殖和活力、极化、细胞周期和凋亡以及包括FAK、桩蛋白和ERK在内的机械转导相关信号分子的活性变化,对液晶底物的储能模量表现出超敏反应。具有12312Pa和7228Pa中间储能模量的辛基羟丙基纤维素底物(分别为OPC-1-5中的OPC-2和OPC-3)可能通过桩蛋白-ERK途径提供更有利的粘附条件,导致更大的铺展面积、更细长的形态和更高的增殖率,而具有最高或最低储能模量的底物(分别为16723Pa,OPC-1;和41Pa,OPC-5)似乎不利于细胞生长。我们的研究为更好地设计生物工程细胞底物的模量驱动细胞行为机制提供了见解。