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活性原细胞中肌动蛋白聚合和对称破缺的合成控制。

Synthetic control of actin polymerization and symmetry breaking in active protocells.

机构信息

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Department of Cell Biology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

出版信息

Sci Adv. 2024 Jun 14;10(24):eadk9731. doi: 10.1126/sciadv.adk9731. Epub 2024 Jun 12.

Abstract

Nonlinear biomolecular interactions on membranes drive membrane remodeling crucial for biological processes including chemotaxis, cytokinesis, and endocytosis. The complexity of biomolecular interactions, their redundancy, and the importance of spatiotemporal context in membrane organization impede understanding of the physical principles governing membrane mechanics. Developing a minimal in vitro system that mimics molecular signaling and membrane remodeling while maintaining physiological fidelity poses a major challenge. Inspired by chemotaxis, we reconstructed chemically regulated actin polymerization inside vesicles, guiding membrane self-organization. An external, undirected chemical input induced directed actin polymerization and membrane deformation uncorrelated with upstream biochemical cues, suggesting symmetry breaking. A biophysical model incorporating actin dynamics and membrane mechanics proposes that uneven actin distributions cause nonlinear membrane deformations, consistent with experimental findings. This protocellular system illuminates the interplay between actin dynamics and membrane shape during symmetry breaking, offering insights into chemotaxis and other cell biological processes.

摘要

细胞膜上的非线性生物分子相互作用驱动了膜重塑,这对于包括趋化作用、胞质分裂和内吞作用在内的生物过程至关重要。生物分子相互作用的复杂性、冗余性以及膜组织中时空背景的重要性,阻碍了对控制膜力学的物理原理的理解。开发一种能够模拟分子信号和膜重塑的最小体外系统,同时保持生理保真度,这是一个重大挑战。受趋化作用的启发,我们在囊泡内重建了化学调控的肌动蛋白聚合,指导膜的自组织。外部无导向的化学输入诱导了与上游生化信号无关的定向肌动蛋白聚合和膜变形,表明对称性被打破。一个包含肌动蛋白动力学和膜力学的生物物理模型表明,不均匀的肌动蛋白分布会导致非线性的膜变形,这与实验结果一致。这个原细胞系统揭示了肌动蛋白动力学和膜形状在对称性破坏过程中的相互作用,为趋化作用和其他细胞生物学过程提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b7b/11168455/b5629a553dc2/sciadv.adk9731-f1.jpg

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