Tozzi Arturo
Center for Nonlinear Science, Department of Physics, University of North Texas, 1155 Union Circle, #311427, Denton, TX, 76203 - 5017, USA.
Eur Biophys J. 2025 Apr 14. doi: 10.1007/s00249-025-01747-x.
Water is central to biological processes not only as a solvent, but also as an agent shaping macromolecular behavior. Insights into water micro assemblies (WMA), defined by transient regions of low-density water (LDW) and high-density water (HDW), have highlighted their potential impact on biological phenomena. LDW, with its structured hydrogen bonding networks and reduced density, stabilizes hydrophobic interfaces and promotes ordered molecular configurations. Conversely, HDW, with its dynamic and flexible nature, facilitates transitions, solute mobility and molecular flexibility. By correlating experimental observations with simulations, we explore the influence of WMA on three key biological processes. In protein folding, LDW may stabilize hydrophobic cores and secondary structures by forming structured exclusion zones, while HDW may introduce dynamic flexibility, promoting the resolution of folding intermediates and leading to dynamic rearrangements. In enzyme catalysis, LDW may form structured hydration shells around active sites stabilizing active sites over longer timescales, while HDW may support substrate access and catalytic flexibility within active sites. In membrane dynamics, LDW may stabilize lipid headgroups, forming structured hydration layers that enhance membrane rigidity and stability, while HDW may ensure the nanosecond-scale flexibility required for vesicle formation and fusion. Across these tree processes, the WMA's energy contributions, timescales and spatial scales align with the forces and dynamics involved, highlighting the role of LDW and HDW in modulating cellular interactions. This perspective holds implications for the design of lab-on-chip devices, advancements in sensor technologies, development of biomimetic membranes for drug delivery, creation of novel therapeutics and deeper understanding of protein misfolding diseases.
水不仅作为溶剂，而且作为塑造大分子行为的介质，在生物过程中起着核心作用。对由低密度水（LDW）和高密度水（HDW）的瞬态区域定义的水微聚集体（WMA）的深入了解，凸显了它们对生物现象的潜在影响。LDW具有结构化的氢键网络且密度降低，它能稳定疏水界面并促进有序的分子构型。相反，HDW具有动态和灵活的特性，有助于转变、溶质迁移和分子灵活性。通过将实验观察结果与模拟相关联，我们探究了WMA对三个关键生物过程的影响。在蛋白质折叠过程中，LDW可能通过形成结构化的排斥区来稳定疏水核心和二级结构，而HDW可能引入动态灵活性，促进折叠中间体的解析并导致动态重排。在酶催化中，LDW可能在活性位点周围形成结构化的水合壳，在更长的时间尺度上稳定活性位点，而HDW可能支持底物进入活性位点并提供催化灵活性。在膜动力学中，LDW可能稳定脂质头部基团，形成增强膜刚性和稳定性的结构化水合层，而HDW可能确保囊泡形成和融合所需的纳秒级灵活性。在这三个过程中，WMA的能量贡献、时间尺度和空间尺度与所涉及的力和动力学相匹配，突出了LDW和HDW在调节细胞相互作用中的作用。这一观点对芯片实验室设备的设计、传感器技术的进步、用于药物递送的仿生膜的开发、新型疗法的创造以及对蛋白质错误折叠疾病的更深入理解都具有启示意义。
