Motor protein traffic regulation by supply–demand balance of resources

Abstract

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.

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

“…The actual distribution of the particles depends strongly on the chosen reservoir geometry [273,274,229,200,196,78].…”

Limited Resources Induce Bistability in Microtubule Length Regulation

“…As seen in theoretical studies on the collective motion of molecular motors, resource limitation affects the density profile on the MT: regions of low and high motor density separate, as a localized domain wall emerges on the MT [16][17][18][19]. This is a direct result of resource limitation and does not rely on the existence of a motor density gradient, as necessary for domain wall localization in the presence of unlimited resources [20][21][22][23].…”

“…This is a direct result of resource limitation and does not rely on the existence of a motor density gradient, as necessary for domain wall localization in the presence of unlimited resources [20][21][22][23]. So far, most work on the role of limited resources has focused on single components of the relevant system [17][18][19][24][25][26][27][28]. Only a few studies have considered simultaneous limitation of two resources [29].…”

Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection

“…During this process, the cytoplasmic microtubules in host cells act as the piping system for viral delivery (22). There is a variety of host proteins participating in the process of cellular transportation, and each protein has its own driving direction (23). Dynein is responsible for the retrograde transport process, which is from the cell membrane to the nucleus (24).…”