Ciandrini Luca, Neri Izaak, Walter Jean Charles, Dauloudet Olivier, Parmeggiani Andrea
DIMNP UMR 5235 & CNRS, Université Montpellier 2, F-34095, Montpellier, France. Laboratoire Charles Coulomb UMR 5221 & CNRS, Université Montpellier 2, F-34095, Montpellier, France.
Phys Biol. 2014 Sep 10;11(5):056006. doi: 10.1088/1478-3975/11/5/056006.
In cells and in in vitro assays the number of motor proteins involved in biological transport processes is far from being unlimited. The cytoskeletal binding sites are in contact with the same finite reservoir of motors (either the cytosol or the flow chamber) and hence compete for recruiting the available motors, potentially depleting the reservoir and affecting cytoskeletal transport. In this work we provide a theoretical framework in which to study, analytically and numerically, how motor density profiles and crowding along cytoskeletal filaments depend on the competition of motors for their binding sites. We propose two models in which finite processive motor proteins actively advance along cytoskeletal filaments and are continuously exchanged with the motor pool. We first look at homogeneous reservoirs and then examine the effects of free motor diffusion in the surrounding medium. We consider as a reference situation recent in vitro experimental setups of kinesin-8 motors binding and moving along microtubule filaments in a flow chamber. We investigate how the crowding of linear motor proteins moving on a filament can be regulated by the balance between supply (concentration of motor proteins in the flow chamber) and demand (total number of polymerized tubulin heterodimers). We present analytical results for the density profiles of bound motors and the reservoir depletion, and propose novel phase diagrams that present the formation of jams of motor proteins on the filament as a function of two tuneable experimental parameters: the motor protein concentration and the concentration of tubulins polymerized into cytoskeletal filaments. Extensive numerical simulations corroborate the analytical results for parameters in the experimental range and also address the effects of diffusion of motor proteins in the reservoir. We then propose experiments for validating our models and discuss how the 'supply-demand' effects can regulate motor traffic also in in vivo conditions.
在细胞和体外实验中，参与生物运输过程的马达蛋白数量并非无限。细胞骨架结合位点与同一有限的马达储备库（胞质溶胶或流动腔室）接触，因此会竞争招募可用的马达，这可能会耗尽储备库并影响细胞骨架运输。在这项工作中，我们提供了一个理论框架，用于从分析和数值上研究马达密度分布以及细胞骨架丝上的拥挤情况如何取决于马达与其结合位点的竞争。我们提出了两个模型，其中有限的进行性马达蛋白沿着细胞骨架丝积极前进，并与马达池持续交换。我们首先研究均匀的储备库，然后考察周围介质中自由马达扩散的影响。我们将最近在流动腔室中驱动蛋白 - 8马达结合并沿着微管丝移动的体外实验装置视为参考情况。我们研究了在丝上移动的线性马达蛋白的拥挤情况如何通过供应（流动腔室中马达蛋白的浓度）和需求（聚合微管蛋白异二聚体的总数）之间的平衡来调节。我们给出了结合马达密度分布和储备库耗尽的分析结果，并提出了新颖的相图，该相图展示了丝上马达蛋白堵塞的形成与两个可调实验参数的函数关系：马达蛋白浓度和聚合成细胞骨架丝的微管蛋白浓度。广泛的数值模拟证实了实验范围内参数的分析结果，并且还研究了储备库中马达蛋白扩散的影响。然后，我们提出了验证我们模型的实验，并讨论了“供需”效应如何在体内条件下调节马达运输。
