Facing the environment: hydrodynamics and confinement modulate molecular motors dynamics

In this thesis we characterize the behavior of molecular motors when the properties of the cytoplasm they displace through are not homogeneous or isotropic. Anisotropies in the cytoplasm can be induced, for example, by net fluxes that can be generated by the displacement of motors themselves as well...

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Bibliographic Details
Author: Malgaretti, Paolo
Format: doctoral thesis
Status:Published version
Publication Date:2013
Country:España
Institution:CBUC, CESCA
Repository:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/133402
Online Access:http://hdl.handle.net/10803/133402
Access Level:Open access
Keyword:Motor molecular
Molecular motor
Acoblament hidrodinàmic
Acoplamiento hidrodinámico
Hydrodynamic coupling
Ciències Experimentals i Matemàtiques
53
Description
Summary:In this thesis we characterize the behavior of molecular motors when the properties of the cytoplasm they displace through are not homogeneous or isotropic. Anisotropies in the cytoplasm can be induced, for example, by net fluxes that can be generated by the displacement of motors themselves as well by other mechanism such as remodeling of the overall cell shape. In the cytoplasm there are many molecules, proteins, vesicles and organelles in suspension. Such a crowded environment develop inhomogeneities in the local properties of the cytoplasm. The different length scales that characterize such inhomogeneities might led to different interplays according to the size of the cargo pulled by motors. For example, suspended particles whose size is much smaller than the cargo size will be experienced by the cargo as an enhancement in the effective viscosity. On the other hand, suspended particles of the same size or bigger than cargoes will develop local structures that affect the space the cargo can explore and will act like a porous medium. In the first chapter we characterize the hydrodynamic coupling generated by an ensemble of molecular motors displacing along a filament. By numerical simulations we show how such a coupling develops. The hydrodynamic coupling between motor relies on the fluid flow generated by motors displacement. We discuss how the hydrodynamic coupling between motors depends upon the boundary conditions provided by different geometries. Motors do not always displace in the same direction, rather cargoes pulled by teams of motors pulling on opposite directions has been observed to undergo a bidirectional motion where the cargo moves back and forth due to the reorganization of the force generated by the motors. In many cases the cargoes motors pull on are vesicles or membrane-embedded organelles. In these cases motors exert force on the cargo by pulling on molecular linkers embedded in the membrane that link the tail of the motors to the membrane. Therefore, the displacement of the linkers in the membrane will lead to a local flow of membrane that can lead to an overall coupling between motors that will sum up to the one generated by the displacement of the motors in the cytoplasm. In the second chapter we develop a coarse grained description of a team of motors pulling on opposite directions that are hydrodynamically coupled. Thanks to our coarse grained model we characterize the overall dynamics of the system and we discuss the peculiar features induced by the hydrodynamic coupling by comparing them against those obtained in the case of rigidly coupled motors. In the third chapter we characterize the dynamics of a single molecular motor displacing in an inhomogeneous environment modeled as a varying section channel. In the limit in which the channel section is smoothly varying it is possible to reduce the overall dynamics to that of a particle moving in a 1D effective potential where the varying confinement enters as an entropic contribution to the overall potential. Using this framework we characterize the dynamics of molecular motors moving according to different schemes. The comparison between the results obtained with the different models allows us to distinguish between general behaviors and model dependent features.