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Interplay between mechanics and chemistry across different scales. from protein to cell dynamics and morphogenesis
Interplay between mechanics and chemistry across different scales. from protein to cell dynamics and morphogenesis
Living organisms actively respond to their surroundings, be it searching for food or escaping from predators. These actions require detecting and processing environmental signals. Microorganisms, such as bacteria or eukaryotic cells, do so via biochemical signaling networks of molecular switches. Then, some of these signaling networks must be capable of detecting mechanical signals and facilitating mechanical responses. This thesis, structured into several chapters, illustrates the consequences of coupling mechanics and chemistry. After giving a general introduction that outlines some of the main results and places them into a broader context, a separate mathematical introduction explains useful analytical tools and methods. This common framework of differential geometry ties together three overarching themes of this thesis, each having two subprojects. Mechanochemical coupling on the microscale. When binding to an elastic membrane, proteins can induce deformations thereof by exerting reciprocal forces. Then, what are the consequences of this effect for reaction kinetics that couple the cytosol to the membrane? Section II.1 “Mechanochemical Coupling between Proteins and Membranes” illustrates how generic interactions between proteins and a membrane not only deform the latter but also lead to nonlinear self-recruitment of proteins from the cytosol to the membrane. With nonlinear reactions being a central theme of pattern-forming systems, external stimuli could, via mechanical cooperativity, drastically change intracellular signaling patterns. In turn, intracellular pattern formation, via protein turnover and reactions, implies particle fluxes—the center of attention in Section II.2 “Protein Fluxes Induce Generic Transport of Cargo”. In particular, in any dense environment such as on the cell membrane, particle fluxes will couple via effective friction, mediated by hydrodynamic interactions or direct interactions among proteins. This leads to a generic diffusiophoretic effect, where protein patterns can transport and even spatially sort entirely unrelated molecules. Taken together, these results suggest that proteins can perform mechanical work without relying on specialized molecular machinery like the actomyosin cytoskeleton. Integrating signals during cell migration. The actomyosin cytoskeleton is, however, indispensable for the migration of cells. To control this machinery, cells integrate external stimuli via several regulatory pathways that involve positive and negative feedback loops. In Section III.1 “Collective Cell Dynamics in Rigid Environments”, these complex regulatory networks are represented in terms of only two feedback loops that allow the (simulated) cells to polarize. Furthermore, this project shows how, under certain conditions, cell motion is equivalent to an entirely different problem: active surface wetting by a liquid droplet. If proteins can deform membranes by binding, then the much larger cells should do the same to a substrate to which they adhere. In fact, cells induce strains and probe their environment by actively pulling and generating traction forces. Section III.2 “Cell Migration and Shape in Soft Environments” takes these traction forces as a premise for studying how substrate deformations affect cell dynamics. In particular, substrate deformations imply local changes in the distance between the surface ligands that a cell can adhere to, thus generating gradients of adhesiveness. Then, cells can trap themselves on very soft substrates by creating adhesive islands and even break rotational symmetry via profound elongation. When present on the same substrate, large populations of cells can exploit these effects to form networks. How anisotropy affects morphogenesis. Breaking rotational symmetry means that cells exert anisotropic tension, showing particularly strong contractility in some chosen direction. Consequently, cellular reorientations can regulate the tension on a tissue level and thereby control tissue shape. Section IV.1 “Collective Cell Migration Affects Morphogenesis” shows how such a reorientation of cells can induce a shape transformation in miniaturized organs. Then, Section IV.2 “Between Morphogenesis and Hydrodynamic Flows” further studies the consequences of cellular anisotropy and mechanics for the hydrodynamics of tissues. One of the main results is that a tension modulation due to cell reorientation is qualitatively different from an isotropic tension modulation by the very direction in which the tissue will move. Interestingly, isotropic contractility gradients can, through the Marangoni effect and hydraulic pressure, lead to a bulging out of the tissue in the most contractile regions. Such effects could also provide a minimal model for active cell cytoskeleton-driven exocytosis. Another result is that elastic tubular shells can break time-reversal symmetry by exhibiting different hysteresis effects, possibly enabling directed transport. Thus, there is much more to discover!
Cell Migration, Pattern Formation, Morphogenesis, Theoretical Biophysics, Diffusiophoresis, Biomechanics
Goychuk, Andriy
2021
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Goychuk, Andriy (2021): Interplay between mechanics and chemistry across different scales: from protein to cell dynamics and morphogenesis. Dissertation, LMU München: Faculty of Physics
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Abstract

Living organisms actively respond to their surroundings, be it searching for food or escaping from predators. These actions require detecting and processing environmental signals. Microorganisms, such as bacteria or eukaryotic cells, do so via biochemical signaling networks of molecular switches. Then, some of these signaling networks must be capable of detecting mechanical signals and facilitating mechanical responses. This thesis, structured into several chapters, illustrates the consequences of coupling mechanics and chemistry. After giving a general introduction that outlines some of the main results and places them into a broader context, a separate mathematical introduction explains useful analytical tools and methods. This common framework of differential geometry ties together three overarching themes of this thesis, each having two subprojects. Mechanochemical coupling on the microscale. When binding to an elastic membrane, proteins can induce deformations thereof by exerting reciprocal forces. Then, what are the consequences of this effect for reaction kinetics that couple the cytosol to the membrane? Section II.1 “Mechanochemical Coupling between Proteins and Membranes” illustrates how generic interactions between proteins and a membrane not only deform the latter but also lead to nonlinear self-recruitment of proteins from the cytosol to the membrane. With nonlinear reactions being a central theme of pattern-forming systems, external stimuli could, via mechanical cooperativity, drastically change intracellular signaling patterns. In turn, intracellular pattern formation, via protein turnover and reactions, implies particle fluxes—the center of attention in Section II.2 “Protein Fluxes Induce Generic Transport of Cargo”. In particular, in any dense environment such as on the cell membrane, particle fluxes will couple via effective friction, mediated by hydrodynamic interactions or direct interactions among proteins. This leads to a generic diffusiophoretic effect, where protein patterns can transport and even spatially sort entirely unrelated molecules. Taken together, these results suggest that proteins can perform mechanical work without relying on specialized molecular machinery like the actomyosin cytoskeleton. Integrating signals during cell migration. The actomyosin cytoskeleton is, however, indispensable for the migration of cells. To control this machinery, cells integrate external stimuli via several regulatory pathways that involve positive and negative feedback loops. In Section III.1 “Collective Cell Dynamics in Rigid Environments”, these complex regulatory networks are represented in terms of only two feedback loops that allow the (simulated) cells to polarize. Furthermore, this project shows how, under certain conditions, cell motion is equivalent to an entirely different problem: active surface wetting by a liquid droplet. If proteins can deform membranes by binding, then the much larger cells should do the same to a substrate to which they adhere. In fact, cells induce strains and probe their environment by actively pulling and generating traction forces. Section III.2 “Cell Migration and Shape in Soft Environments” takes these traction forces as a premise for studying how substrate deformations affect cell dynamics. In particular, substrate deformations imply local changes in the distance between the surface ligands that a cell can adhere to, thus generating gradients of adhesiveness. Then, cells can trap themselves on very soft substrates by creating adhesive islands and even break rotational symmetry via profound elongation. When present on the same substrate, large populations of cells can exploit these effects to form networks. How anisotropy affects morphogenesis. Breaking rotational symmetry means that cells exert anisotropic tension, showing particularly strong contractility in some chosen direction. Consequently, cellular reorientations can regulate the tension on a tissue level and thereby control tissue shape. Section IV.1 “Collective Cell Migration Affects Morphogenesis” shows how such a reorientation of cells can induce a shape transformation in miniaturized organs. Then, Section IV.2 “Between Morphogenesis and Hydrodynamic Flows” further studies the consequences of cellular anisotropy and mechanics for the hydrodynamics of tissues. One of the main results is that a tension modulation due to cell reorientation is qualitatively different from an isotropic tension modulation by the very direction in which the tissue will move. Interestingly, isotropic contractility gradients can, through the Marangoni effect and hydraulic pressure, lead to a bulging out of the tissue in the most contractile regions. Such effects could also provide a minimal model for active cell cytoskeleton-driven exocytosis. Another result is that elastic tubular shells can break time-reversal symmetry by exhibiting different hysteresis effects, possibly enabling directed transport. Thus, there is much more to discover!