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正协同作用驱动的膜表面聚合物缩合的灵敏和选择性。

Sensitive and selective polymer condensation at membrane surface driven by positive co-operativity.

机构信息

Department of Physics, Boston University, Boston, MA 02215.

Department of Chemistry, University of Wisconsin, Madison, WI 53706.

出版信息

Proc Natl Acad Sci U S A. 2023 Apr 11;120(15):e2212516120. doi: 10.1073/pnas.2212516120. Epub 2023 Apr 5.

Abstract

Biomolecular phase separation has emerged as an essential mechanism for cellular organization. How cells respond to environmental stimuli in a robust and sensitive manner to build functional condensates at the proper time and location is only starting to be understood. Recently, lipid membranes have been recognized as an important regulatory center for biomolecular condensation. However, how the interplay between the phase behaviors of cellular membranes and surface biopolymers may contribute to the regulation of surface condensation remains to be elucidated. Using simulations and a mean-field theoretical model, we show that two key factors are the membrane's tendency to phase-separate and the surface polymer's ability to reorganize local membrane composition. Surface condensate forms with high sensitivity and selectivity in response to features of biopolymer when positive co-operativity is established between coupled growth of the condensate and local lipid domains. This effect relating the degree of membrane-surface polymer co-operativity and condensate property regulation is shown to be robust by different ways of tuning the co-operativity, such as varying membrane protein obstacle concentration, lipid composition, and the affinity between lipid and polymer. The general physical principle emerged from the current analysis may have implications in other biological processes and beyond.

摘要

生物分子相分离已成为细胞组织的基本机制。细胞如何以稳健和敏感的方式响应环境刺激,在适当的时间和地点构建功能性凝聚体,这才刚刚开始被理解。最近,脂质膜已被认为是生物分子凝聚的一个重要调控中心。然而,细胞膜的相行为和表面生物聚合物之间的相互作用如何有助于表面凝聚的调节,仍有待阐明。我们使用模拟和平均场理论模型表明,两个关键因素是膜的相分离趋势和表面聚合物重组局部膜组成的能力。当凝聚物和局部脂质区域的耦合生长之间建立正协同作用时,表面凝聚物会对生物聚合物的特征表现出高灵敏度和选择性。通过改变协同作用的不同方式,如改变膜蛋白障碍物浓度、脂质组成以及脂质和聚合物之间的亲和力,这种与膜-表面聚合物协同作用程度和凝聚物性质调节相关的效应被证明是稳健的。当前分析中出现的一般物理原理可能在其他生物过程中乃至更广泛的领域中具有意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5305/10104518/b0ed5a4c77d6/pnas.2212516120fig01.jpg

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