Two-dimensional molecular condensation in cell signaling and mechanosensing

Acta Biochim Biophys Sin (Shanghai). 2023 Jul 20;55(7):1064-1074. doi: 10.3724/abbs.2023132.

Abstract

Membraneless organelles (MLO) regulate diverse biological processes in a spatiotemporally controlled manner spanning from inside to outside of the cells. The plasma membrane (PM) at the cell surface serves as a central platform for forming multi-component signaling hubs that sense mechanical and chemical cues during physiological and pathological conditions. During signal transduction, the assembly and formation of membrane-bound MLO are dynamically tunable depending on the physicochemical properties of the surrounding environment and partitioning biomolecules. Biomechanical properties of MLO-associated membrane structures can control the microenvironment for biomolecular interactions and assembly. Lipid-protein complex interactions determine the catalytic region's assembly pattern and assembly rate and, thereby, the amplitude of activities. In this review, we will focus on how cell surface microenvironments, including membrane curvature, surface topology and tension, lipid-phase separation, and adhesion force, guide the assembly of PM-associated MLO for cell signal transductions.

Keywords: mechanosensing; membrane-bound MLO; signal transduction; two-dimensional molecular condensation.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomolecular Condensates* / physiology
  • Cell Adhesion
  • Cell Membrane* / physiology
  • Mechanotransduction, Cellular*
  • Membrane Lipids

Substances

  • Membrane Lipids

Grants and funding

This work was supported by the grants from the Human Frontier Science Program Foundation (No. RGY0088/2021 to W.Z.), the Start-up Grant from Nanyang Technological University to W.Z., Ministry of Education, Singapore (Nos. RG112/20, RG95/21, RG93/22, MOE-MOET32020-0001 to W.Z.), National Research Foundation, Singapore (No. NRF2019-NRF-ISF003-3292 to W.Z.), Singapore MOE Tier 2 (Nos. MOE-T2EP30121-0015 and MOE-T2EP30122-0021 to Y.M.), MOE Tier 3 (No. MOE2019-T3-1-012 to Y.M.), National Research Foundation Singapore under its Open Fund-Individual Research Grant (No. MOH-000955 to Y.M.), and National Research Foundation-Quantum Sensors for Health and Life Sciences (No. NRF2021-QEP2-03-P10 to Y.M.).