Mechanisms of actin-based force generation, morphodynamics and motility of single cells

细胞在胚胎发生、伤口愈合或肿瘤转移过程中爬行。在许多细胞类型和运动的许多阶段中，产生运动的力是通过在膜突起如伪足、板状伪足或神经元的生长锥中的肌动蛋白丝的聚合来建立的。同样的过程也驱动细胞形态动力学。目前的项目研究如何肌动蛋白聚合产生的力量，导致细胞运动和形态动力学。将使用扫描力显微镜以恒定和位置相关力测量力-速度关系。我们还将监测逆行肌动蛋白流的功能和行为。调节肌动蛋白丝成核和交联将揭示这些参数和网络连接的程度对细胞边缘突起和力产生的机械性能的影响。所有的实验都将得到数学建模的支持，并将根据数学模型定量地制定机制假设。

Cells crawl during embryogenesis, wound healing or tumor metastasis. In many cell types and in many phases of motility, the force generating motion is established by the polymerization of actin filaments in membrane protrusions like pseudopodia, lamellipodia or growth cones of neurons. The same processes also drive cellular morphodynamics. The current project investigates how actin polymerization generates the force causing cell motion and morphodynamics. The force-velocity-relation will be measured with constant and position-dependent force using scanning force microscopy. We will also monitor function and behavior of retrograde actin flow. Modulating actin filament nucleation and cross-linking will reveal the impact of these parameters and of the degree of network connectivity on the mechanical properties of cell edge protrusion and force generation. All experiments will be supported by mathematical modeling, and hypotheses on mechanisms will be quantitatively formulated in terms of mathematical models.