核层-A尺度具有组织硬性,并增强矩阵导向差异化
Joe Swift1, Irena L Ivanovska, Amnon Buxboim
1Molecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.
概括
组织硬度和应力通过控制层状A蛋白水平来调节干细胞分化. 较高的分层-A促进骨形成,而较低的水平有利于脂肪的发展,影响血统的确定.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 生物材料科学 生物材料科学
背景情况:
- 组织机制,从软脂肪到硬骨,有很大的不同.
- 组织机械特性与干细胞分化之间的关系尚不清楚.
- 细胞对机械线索的反应对发育和疾病至关重要.
研究的目的:
- 研究组织力学与干细胞分化之间的系统关系.
- 确定关键的分子参与者,调解机械性质对细胞命运的影响.
- 阐明了lamin-A在将机械线索与血统确定中的作用.
主要方法:
- 蛋白质组学分析以量化与组织弹性相关的蛋白质水平.
- 在不同硬度的矩阵上进行体外干细胞分化试验.
- 西部涂抹和免疫光检测以评估层状A蛋白水平和局部化.
- 视网膜酸 (RA) 信号通路组件的调制.
主要成果:
- 拉敏A蛋白水平与组织弹性 (E) 和原含量直接相关.
- 软矩阵低层-A增强脂肪生成 (脂肪分化).
- 具有高层-A的刚性矩阵促进了骨质生成 (骨分化).
- 矩阵刚度调节了拉米尼-A蛋白水平,拉米尼-A影响了视网膜酸受体的核入口.
结论:
- 组织刚性和机械应力是通过层A进行干细胞分化的关键调节剂.
- 拉米纳-A作为一个机械传感器,将物理线索与分子信号通路连接起来.
- 这种机制为理解机械力如何指导组织发育和平衡提供了一个框架.
相关概念视频
Laminins are the Adhesive Proteins of Basal Lamina
Laminins are heterotrimeric proteins with high molecular mass found in the extracellular matrix. Each laminin molecule is composed of three chains, viz. alpha, beta, and gamma, coded by five, four, and three paralogous genes, respectively. Laminins are categories based on the compositions of the three chains.
In humans, the five forms of alpha chains are LAMA 1, LAMA 2, LAMA 3, LAMA 4, and LAMA 5. The four forms of beta chains are LAMB 1, LAMB 2, LAMB 3, and LAMB 4. The three forms of gamma...
In humans, the five forms of alpha chains are LAMA 1, LAMA 2, LAMA 3, LAMA 4, and LAMA 5. The four forms of beta chains are LAMB 1, LAMB 2, LAMB 3, and LAMB 4. The three forms of gamma...
Cell-matrix's Response to Mechanical Forces
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
Disassembly of Intermediate Filaments
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Basal Lamina are the Specialized Form of ECM
The basal lamina is a thin extracellular layer that lies underneath the cells and separates them from other tissues. The three layers of the basal lamina are lamina lucida, lamina densa and lamina reticularis. The basal lamina, a mixture of glycoproteins and collagen, provides an attachment site for the epithelium, separating it from underlying connective tissue. The framework of basal lamina has other essential proteins such as laminins mesh, perlecan, entactin, and type IV collagen.
Proteins...
Proteins...
Overview of Cell-Matrix Interactions
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
Mechanism of Lamellipodia Formation
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...


