Force sharing and force generation by two teams of elastically coupled molecular motors

Abstract

Many active cellular processes such as long-distance cargo transport, spindle organization, as well as flagellar and ciliary beating are driven by molecular motors. These motor proteins act collectively and typically work in small teams. One particularly interesting example is two teams of antagonistic motors that pull a common cargo into opposite directions, thereby generating mutual interaction forces. Important issues regarding such multiple motor systems are whether or not motors from the same team share their load equally, and how the collectively generated forces depend on the single motor properties. Here we address these questions by introducing a stochastic model for cargo transport by an arbitrary number of elastically coupled molecular motors. We determine the state space of this motor system and show that this space has a rather complex and nested structure, consisting of multiple activity states and a large number of elastic substates, even for the relatively small system of two identical motors working against one antagonistic motor. We focus on this latter case because it represents the simplest tug-of-war that involves force sharing between motors from the same team. We show that the most likely motor configuration is characterized by equal force sharing between identical motors and that the most likely separation of these motors corresponds to a single motor step. These likelihoods apply to different types of motors and to different elastic force potentials acting between the motors. Furthermore, these features are observed both in the steady state and during the initial build-up of elastic strains. The latter build-up is non-monotonic and exhibits a maximum at intermediate times, a striking consequence of mutual unbinding of the elastically coupled motors. Mutual strain-induced unbinding also reduces the magnitude of the collectively generated forces. Our computational approach is quite general and can be extended to other motor systems such as motor teams working against an optical trap or mixed teams of motors with different single motor properties.

Tug-of-War and Coordination in Bidirectional Transport by Molecular Motors

“…Other variants of tug-of-war models have considered the effects on force fluctuations and unequal force distribution. [20][21][22][23][24][25]35 If we define F ± as the loads on the plus and minus motors, respectively, then our assumptions lead to the force balance for the state (n…”

Measuring force generation within reconstituted microtubule bundle assemblies using optical tweezers

“…In complex environments like the mitotic spindle, microtubules are in both parallel and anti‐parallel orientations, and activity in such environments reveals unique location‐specific roles that motors play to build the spindle and balance forces. Behaviors of kinesin‐MT bundles have also been investigated computationally, especially to shed light on motor cooperativity that accomplishes force generation and thus cargo movement (Blackwell et al, 2017; Chowdhury & Ghanti, 2020; Edelmaier et al, 2020; Kapoor, Hirst, Hentschel, Preibisch, & Reber, 2019; Lera‐Ramirez & Nédélec, 2019; Prelogovic, Winters, Milas, Tolic, & Pavin, 2019; Sherin, Farwa, Sohail, Li, & Bég, 2018; Uçar & Lipowsky, 2019; Winters et al, 2019; Zemel & Mogilner, 2009; Ziebert, Vershinin, Gross, & Aranson, 2009). Using this approach, theorists and experimentalists are able to work together to reconcile to what degree motors are synergistically coupled and how their structural features facilitate the experimental results obtained.…”

Cooperation and competition in the collective drive by motor proteins: mean active force, fluctuations, and self-load

“…49,50 Cooperation and competition between MPs in driving cargo generate rich dynamics. [53][54][55][56][57][58][59][60] In a large assembly of F-actins or microtubules driven by such an MP bed of conjugate MPs, intriguing collective motion, including gliding, swirling, and spiral formation was observed. [61][62][63][64] The motion of MP-driven semiflexible filaments led to several remarkable properties, including dynamical transitions between spiral and open chain conformations.…”