Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 2019 Aug 27;116(35):17175-17180. doi: 10.1073/pnas.1903890116. Epub 2019 Aug 13.
In many developmental and pathological processes, including cellular migration during normal development and invasion in cancer metastasis, cells are required to withstand severe deformations. The structural integrity of eukaryotic cells under small deformations has been known to depend on the cytoskeleton including actin filaments (F-actin), microtubules (MT), and intermediate filaments (IFs). However, it remains unclear how cells resist severe deformations since both F-actin and microtubules yield or disassemble under moderate strains. Using vimentin containing IFs (VIFs) as a model for studying the large family of IF proteins, we demonstrate that they dominate cytoplasmic mechanics and maintain cell viability at large deformations. Our results show that cytoskeletal VIFs form a stretchable, hyperelastic network in living cells. This network works synergistically with other cytoplasmic components, substantially enhancing the strength, stretchability, resilience, and toughness of cells. Moreover, we find the hyperelastic VIF network, together with other quickly recoverable cytoskeletal components, forms a mechanically robust structure which can mechanically recover after damage.
在许多发育和病理过程中,包括正常发育过程中的细胞迁移和癌症转移中的侵袭,细胞都需要经受严重的变形。在小变形下,真核细胞的结构完整性已知依赖于细胞骨架,包括肌动蛋白丝(F-actin)、微管(MT)和中间丝(IFs)。然而,目前尚不清楚细胞如何抵抗严重的变形,因为在中等应变下 F-actin 和微管都会产生或解体。我们使用含有中间丝(VIFs)的波形蛋白作为研究中间丝蛋白大家族的模型,证明它们主导细胞质力学,并在大变形下维持细胞活力。我们的结果表明,细胞骨架中的 VIF 形成了一个可拉伸的超弹性网络。该网络与其他细胞质成分协同作用,显著提高了细胞的强度、可拉伸性、弹性和韧性。此外,我们发现超弹性 VIF 网络与其他快速可恢复的细胞骨架成分一起形成了一种机械坚固的结构,在受到损伤后可以进行机械恢复。