软相互作用和束缚流动性对拥挤环境中扩散的影响:粘性和滑性障碍物模型

Effects of soft interactions and bound mobility on diffusion in crowded environments: a model of sticky and slippery obstacles.

作者信息

Stefferson Michael W, Norris Samantha L, Vernerey Franck J, Betterton Meredith D, Hough Loren E

机构信息

Department of Physics, University of Colorado, Boulder, United States of America.

出版信息

Phys Biol. 2017 Jun 29;14(4):045008. doi: 10.1088/1478-3975/aa7869.

Abstract

Crowded environments modify the diffusion of macromolecules, generally slowing their movement and inducing transient anomalous subdiffusion. The presence of obstacles also modifies the kinetics and equilibrium behavior of tracers. While previous theoretical studies of particle diffusion have typically assumed either impenetrable obstacles or binding interactions that immobilize the particle, in many cellular contexts bound particles remain mobile. Examples include membrane proteins or lipids with some entry and diffusion within lipid domains and proteins that can enter into membraneless organelles or compartments such as the nucleolus. Using a lattice model, we studied the diffusive movement of tracer particles which bind to soft obstacles, allowing tracers and obstacles to occupy the same lattice site. For sticky obstacles, bound tracer particles are immobile, while for slippery obstacles, bound tracers can hop without penalty to adjacent obstacles. In both models, binding significantly alters tracer motion. The type and degree of motion while bound is a key determinant of the tracer mobility: slippery obstacles can allow nearly unhindered diffusion, even at high obstacle filling fraction. To mimic compartmentalization in a cell, we examined how obstacle size and a range of bound diffusion coefficients affect tracer dynamics. The behavior of the model is similar in two and three spatial dimensions. Our work has implications for protein movement and interactions within cells.

摘要

拥挤的环境会改变大分子的扩散,通常会减缓它们的运动并引发瞬时反常亚扩散。障碍物的存在也会改变示踪剂的动力学和平衡行为。虽然先前关于粒子扩散的理论研究通常假设存在不可穿透的障碍物或使粒子固定的结合相互作用,但在许多细胞环境中,结合的粒子仍然是可移动的。例子包括在脂质域内具有一定进入和扩散能力的膜蛋白或脂质,以及能够进入无膜细胞器或隔室(如核仁)的蛋白质。我们使用晶格模型研究了与软障碍物结合的示踪粒子的扩散运动,允许示踪剂和障碍物占据相同的晶格位点。对于粘性障碍物,结合的示踪粒子是固定的,而对于光滑障碍物,结合的示踪剂可以无阻碍地跳跃到相邻障碍物上。在这两种模型中,结合都会显著改变示踪剂的运动。结合时的运动类型和程度是示踪剂迁移率的关键决定因素:即使在高障碍物填充率下,光滑障碍物也能允许几乎不受阻碍的扩散。为了模拟细胞中的区室化,我们研究了障碍物大小和一系列结合扩散系数如何影响示踪剂动力学。该模型在二维和三维空间中的行为相似。我们的工作对细胞内蛋白质的运动和相互作用具有启示意义。

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