Recent studies indicate that extracellular mechanical properties, including rigidity, profoundly affect cellular morphology, growth, migration, and differentiation [R. J. Pelham, Jr. and Y. Wang, Proc. Natl. Acad. Sci. U. S. A., 1997, >94(25), 13661–13665; H. B. Wang, M. Dembo and Y. L. Wang, Am. J. Physiol. Cell Physiol., 2000, >279(5), C1345–C1350; P. C. Georges, and P. A. Janmey, J. Appl. Physiol., 2005, >98(4), 1547–1553; C. M. Lo, H. B. Wang, M. Dembo and Y. L. Wang, Biophys. J., 2000. >79(1), 144–152; D. E. Discher, P. Janmey and Y. L. Wang, Science, 2005, >310(5751), 1139–1143; A. J. Engler, M. A. Griffin, S. Sen, C. G. Bonnemann, H. L. Sweeney and D. E. Discher, J. Cell Biol., 2004, >166(6), 877–887]. However, most studies involving rigidity sensing have been performed by comparing cells on separate substrata of fixed stiffness. To allow spatial and/or temporal manipulation of mechanical properties, we have developed a modulatable hydrogel by reacting linear polyacrylamide (PA) with a photosensitive crosslinker. This material allows UV-mediated control of rigidity, softening by 20–30% upon irradiation at a dose tolerated by live cells. Global UV irradiation induces an immediate recoiling of 3T3 fibroblasts and a reduced spread area at steady state. Furthermore, localized softening of the posterior substratum of polarized cells causes no apparent effect, while softening of the anterior substratum elicits pronounced retraction, indicating that rigidity sensing is localized to the frontal region. This type of material allows precise spatial and temporal control of mechanical signals for both basic research and regenerative medicine.
展开▼
机译:最近的研究表明,包括刚性在内的细胞外机械性能会深刻影响细胞的形态,生长,迁移和分化[R。 J. Pelham,Jr.和Y. Wang,Proc。 Natl。学院科学U. S. A.,1997,> 94 strong>(25),13661–13665; H.B. Wang,M.Dembo和Y.L.Wang,Am。 J.生理学。细胞生理学,2000,> 279 strong>(5),C1345–C1350; P.C. Georges和P.A.Janmey,J.Appl。生理学杂志,2005,> 98 strong>(4),1547–1553; C.M. Lo,H.B.Wang,M.Dembo和Y.L.Wang,Biophys。 J.,2000。> 79 strong>(1),144-152; D. E. Discher,P。Janmey和Y.L. Wang,《科学》,2005年,> 310 strong>(5751),1139–1143; A. J. Engler,M。A. Griffin,S。Sen,C。G. Bonnemann,H。L. Sweeney和D. E. Discher,J。Cell Biol。,2004,> 166 strong>(6),877-887]。但是,大多数涉及刚度传感的研究都是通过比较固定刚度的单独底层上的单元格进行的。为了允许在空间和/或时间上控制机械性能,我们通过使线性聚丙烯酰胺(PA)与光敏交联剂反应,开发了可调节的水凝胶。这种材料可以通过紫外线介导的硬度控制,以活细胞耐受的剂量照射后可软化20–30%。整体紫外线照射可立即卷起3T3成纤维细胞,并在稳态下减少扩散面积。此外,极化细胞后基质的局部软化不会产生明显的影响,而前基质的软化则引起明显的回缩,这表明刚度感应局限于额叶区域。这种材料可以对基础研究和再生医学的机械信号进行精确的时空控制。
展开▼