Department of Biochemistry, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo Foundation, University of Pavia, Pavia, Italy.
Blood. 2011 Oct 20;118(16):4449-53. doi: 10.1182/blood-2011-04-345876. Epub 2011 Aug 9.
Cell interactions with matrices via specific receptors control many functions, with chemistry, physics, and membrane elasticity as fundamental elements of the processes involved. Little is known about how biochemical and biophysical processes integrate to generate force and, ultimately, to regulate hemopoiesis into the bone marrow-matrix environment. To address this hypothesis, in this work we focus on the regulation of MK development by type I collagen. By atomic force microscopy analysis, we demonstrate that the tensile strength of fibrils in type I collagen structure is a fundamental requirement to regulate cytoskeleton contractility of human MKs through the activation of integrin-α2β1-dependent Rho-ROCK pathway and MLC-2 phosphorylation. Most importantly, this mechanism seemed to mediate MK migration, fibronectin assembly, and platelet formation. On the contrary, a decrease in mechanical tension caused by N-acetylation of lysine side chains in type I collagen completely reverted these processes by preventing fibrillogenesis.
细胞通过特定的受体与基质相互作用，控制着许多功能，其中化学、物理和膜弹性是涉及过程的基本要素。人们对于生化和生物物理过程如何整合产生力，最终调节造血进入骨髓基质环境知之甚少。为了解决这个假设，在这项工作中，我们专注于 I 型胶原对 MK 发育的调节。通过原子力显微镜分析，我们证明了 I 型胶原结构中纤维的拉伸强度是通过激活整合素-α2β1 依赖性 Rho-ROCK 途径和 MLC-2 磷酸化来调节人 MK 细胞骨架收缩性的基本要求。最重要的是，这种机制似乎介导了 MK 的迁移、纤维连接蛋白的组装和血小板的形成。相反，I 型胶原赖氨酸侧链 N-乙酰化导致的机械张力降低，通过阻止纤维形成，完全逆转了这些过程。
