Self-organization pathways in active filament bundles

Striebel, Moritz (2023): Self-organization pathways in active filament bundles. Dissertation, LMU München: Fakultät für Physik

Abstract

Living cells rely on the active remodeling of cytoskeletal structures. This remodeling is mediated by the interaction of filaments with a variety of different associated proteins, most importantly motor proteins. Motor proteins operate by using chemical energy to generate force and movement. Thus, filament-motor-mixtures are a paradigmatic example of out-of-equilibrium physics. The transduction of chemical energy enables filament-motor-mixtures to obtain spatial and temporal organization. How interactions between motor proteins and cytoskeletal filaments, which happen on the nanometer scale, can give rise to spatial organization on the scale of up to hundreds of micrometers is the main focus of this thesis. To approach this question, I studied two typical interactions between motor proteins and cytoskeletal filaments: First, motor-mediated length regulation of filaments in chapter 2, and second, motor-mediated force generation in chapter 3. In the chapter Collective filament length regulation in filament-motor mixtures, we study a minimal biophysical model for motor-mediated filament length regulation in an ensemble of kinesin-8 motors and microtubules. Importantly, we account explicitly for the diffusive redistribution of cytosolic tubulin and kinesin-8 motors. We derive a hydrodynamic description of the model on the basis of time and length scale separation arguments. Our theoretic description is accompanied by large-scale computer simulations. Strikingly, we find that, even though filaments interact only indirectly via a shared pool of resources, the filament-motor-mixture is capable of self-organizing into structures that span multiple filament lengths and show aster-like orientational order. In the subsequent section, we formalize our theoretical approach and perform a moment and gradient expansion to derive our hydrodynamic theory. Using agent-based simulations, we study the long term dynamics of the system on a phenomenological level and find spontaneous symmetry breaking in the orientational order, traveling wave solutions, coalescence and coarsening of the emerging filament structures. In the chapter Collective filament motion in active filament bundles, we investigate emergent collective dynamics in filament bundles cross-linked by motor proteins that exert mechanical forces on the filaments. Starting from a microscopic model and based on a time-scale separation argument, we derive a coarse-grained filament-filament interaction. Based on this filament filament interaction, we study the collective interplay between motor-generated forces and filament bundle dynamics. In the first section, we study a bundle of filaments that are cross-linked by a set of motors and ask which mechanisms control the filament bundles’ propensity to contract or expand. Based on a generic model for motor cross-linkers, we derive a formalism to quantify the active tension in a bundle of cross-linked filaments. Using this generic model, we study a system composed of filaments, passive bundling agents, and cross-linking motors that can dwell at the filament tip. In this system, we identify three external control parameters that regulate the filament bundles’ propensity to contract or expand: First, the total number of motors in the system. Second, the total number of bundling agents, and third, the filament length. We validate our theoretical predictions and study the emergent long-term dynamics of the filament bundle using agent-based simulations. Our predictions are in accordance with recent in vitro experiments. In the following sections, we addressed the question of how motor cross-linkers control the filament sliding speed in a bundle of cross-linked filaments. On the microscopic scale, motor-generated filament motion seems to be inherently linked to the relative orientation of cross linked filaments. However, in vivo and in vitro observations in the mitotic spindle demonstrated that the speed of filament sliding is independent of the local number of interaction partners with equal and opposite orientations. Motivated by this apparent contradiction, we sought to understand which processes regulate collective filament sliding in active nematic networks. We identified a mechanism for collective filament sliding: Owing to the cross-linking in the filament network, the locally generated force can be propagated through the network over a characteristic length scale. This length scale is set by the antagonism between dissipation to the surrounding fluid and active motor-driven forces imposed on the filament. We then proceeded to study how the identified mechanism depends on the connectivity of the filament network with the help of large-scale computer simulations. Taken together, we have studied how interactions of motor proteins and filaments, which take place on the nanometer scale, affect the emergent collective dynamics of filament-motor-mixtures on the scale of micrometers. We have shown that the active, motor-mediated depolymerization of filaments, in combination with mass conservation, does not only control the size of emergent filament structures but provides a self-organization pathway on its own. In bundles of filaments cross-linked by motor proteins capable of exerting mechanical force, we have shown how the active tension and the sliding speed of filaments depend on the kinetic and mechanical properties of the cross-linking motor proteins. Thereby, our work clarifies why some motor cross-linkers cause filament network contraction while others promote extensile tension in filament-motor mixtures. In the living cell, motor-mediated filament length regulation and motor-mediated mechanical interactions between filaments are no isolated processes – they take place simultaneously. It will be an interesting avenue for future research to understand the collective dynamics of filament-motor-mixtures where both motor-mediated mechanical filament-filament interactions and length regulation are present.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 530 Physik
• Fakultäten: Fakultät für Physik
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 9. November 2023
• 1. Bericht­erstatter:in: Frey, Erwin