Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA.
Nanobiology Institute, Yale University, West Haven, CT 06516, USA.
Sci Adv. 2023 Oct 13;9(41):eadi1535. doi: 10.1126/sciadv.adi1535.
Forces are central to countless cellular processes, yet in vivo force measurement at the molecular scale remains difficult if not impossible. During clathrin-mediated endocytosis, forces produced by the actin cytoskeleton are transmitted to the plasma membrane by a multiprotein coat for membrane deformation. However, the magnitudes of these forces remain unknown. Here, we present new in vivo force sensors that induce protein condensation under force. We measured the forces on the fission yeast Huntingtin-Interacting Protein 1 Related (HIP1R) homolog End4p, a protein that links the membrane to the actin cytoskeleton. End4p is under ~19-piconewton force near the actin cytoskeleton, ~11 piconewtons near the clathrin lattice, and ~9 piconewtons near the plasma membrane. Our results demonstrate that forces are collected and redistributed across the endocytic machinery.
力在无数细胞过程中起着核心作用，但在体内对分子尺度的力进行测量仍然很困难，如果不是不可能的话。在网格蛋白介导的胞吞作用中，由肌动蛋白细胞骨架产生的力通过一个多蛋白外壳传递到质膜，用于膜变形。然而，这些力的大小仍然未知。在这里，我们提出了新的体内力传感器，在力的作用下诱导蛋白质凝聚。我们测量了与膜连接到肌动蛋白细胞骨架的 fission yeast Huntingtin-Interacting Protein 1 Related (HIP1R) 同源物 End4p 的力。End4p 在靠近肌动蛋白细胞骨架的地方受到约 19 皮牛顿的力，在靠近网格蛋白晶格的地方受到约 11 皮牛顿的力，在靠近质膜的地方受到约 9 皮牛顿的力。我们的结果表明，力被收集并在胞吞机制中重新分配。
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