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Theoretical study of active gel dynamics in evolving domains using phase fields

Applicant Kruse Karsten
Number 175996
Funding scheme Project funding (Div. I-III)
Research institution Département de Biochimie Faculté des Sciences II Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Theoretical Physics
Start/End 01.12.2017 - 30.11.2021
Approved amount 650'000.00
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All Disciplines (3)

Discipline
Theoretical Physics
Biophysics
Cellular Biology, Cytology

Keywords (11)

cytoskeleton; actin; cell division; cell migration; blebs; active matter; non-equilibrium physics; collective phenomena; self-organization; phase fields; spontaneous waves

Lay Summary (German)

Lead
Das Aktin-Zytoskelett, ein Netzwerk fadenförmiger Proteine, spielt eine wesentliche Rolle in lebenswichtigen zellulären Prozesses wie der Zellteilung und -bewegung und bestimmt die mechanischen Eigenschaften vieler Zelltypen. Diese Prozesse werden durch die Umwandlung chemischer Energie in mechanische Arbeit getrieben. Vom Standpunkt der Physik gehört das Zytoskelett somit zu den aktiven Gelen. In der Vergangenheit sind verschiedene physikalische Ansätze zu deren Beschreibung entwickelt worden. Die Analyse dieser Beschreibungen ist bisher hauptsächlich auf statische Gebiete beschränkt. Zellen hingegen ändern ihre Form während der Zellteilung und -bewegung.
Lay summary
Inhalt und Ziel des Forschungsprojekts 

Das Ziel dieses Projekts ist es, die Dynamik aktiver Gele in veränderlichen Geometrien zu untersuchen. Damit soll der Einfluss des Zytoskeletts auf die Zellform und umgekehrt charakterisiert werden. Die dynamische Zellform werden wir dabei durch Phasenfelder beschreiben, die verschiedene Werte in- und außerhalb der Zelle annehmen. Im einzelnen werden wir (i) die Zellbewegung durch spontane Aktinwellen betrachten, (ii) die Stabilität des Aktin-Cortex, einer dünnen Aktinschicht unterhalb der Zellmembran, analysieren und (iii) eine physikalische Beschreibung sogenannter Blebs entwickeln. Letztere sind kurzlebige Ablösungen der Membran vom Aktin-Cortex und treten u.a. bei der Teilung und Migration von Zellen auf. 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Unsere Arbeit wird einen Rahmen für die Beschreibung zellulärer Morphogenese unter Benutzung von Phasenfeldern entwickeln. Damit werden wir wertvolle Erkenntnisse über die Rolle spontaner, also physikalischer Prozesse für das Verhalten von Zellen und für zelluläre Formänderungen gewinnen. Diese werden neue Impulse für die Berücksichtigung physikalischer Mechanismen in der Analyse physiologische Prozesse liefern. 
Direct link to Lay Summary Last update: 23.10.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
Deterministic actin waves as generators of cell polarization cues
Stankevicins Luiza, Ecker Nicolas, Terriac Emmanuel, Maiuri Paolo, Schoppmeyer Rouven, Vargas Pablo, Lennon-Duménil Ana-Maria, Piel Matthieu, Qu Bin, Hoth Markus, Kruse Karsten, Lautenschläger Franziska (2020), Deterministic actin waves as generators of cell polarization cues, in Proceedings of the National Academy of Sciences, 117(2), 826-835.
Spontaneous formation of chaotic protrusions in a polymerizing active gel layer
Levernier N, Kruse K (2020), Spontaneous formation of chaotic protrusions in a polymerizing active gel layer, in New Journal of Physics, 22(1), 013003.
Aurora A depletion reveals centrosome-independent polarization mechanism in Caenorhabditis elegans
Klinkert Kerstin, Levernier Nicolas, Gross Peter, Gentili Christian, von Tobel Lukas, Pierron Marie, Busso Coralie, Herrman Sarah, Grill Stephan W, Kruse Karsten, Gönczy Pierre (2019), Aurora A depletion reveals centrosome-independent polarization mechanism in Caenorhabditis elegans, in eLife, 8, e44552.

Collaboration

Group / person Country
Types of collaboration
Marco Fritzsche, University Oxford Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Franziska Lautenschläger, Saarland University Germany (Europe)
- Publication
Pierre Gönczy, EPFL Switzerland (Europe)
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Dynamics Days Digital Talk given at a conference Deterministic actin waves as generators of cell polarization cues 24.08.2020 internet, France Kruse Karsten;
Cell Physics Poster A phase-field approach for studying actin-wave driven cell migration 09.10.2019 Saarbrücken, Germany Ecker Nicolas;
Circle meeting Talk given at a conference Collective cell migration driven by spontaneous actin waves 27.03.2019 Saarbrücken, Germany Ecker Nicolas;
APS March Meeting Talk given at a conference Dynamic instabilities of contractile actomyosin rings 04.03.2019 Boston, United States of America Kruse Karsten;
GRC on Oscillations and Dynamic Instabilities Talk given at a conference Chemomechanical Oscillations in Polymerizing Actin Networks 08.07.2018 Les Diablerets, Switzerland Kruse Karsten;
Geneva chemistry and biochemistry days Talk given at a conference spontaneous actin polymerization waves and cell migration 18.01.2018 Geneva, Switzerland Ecker Nicolas;


Awards

Title Year
Prix Bettencourt pour les jeunes chercheurs - 2018 2019

Associated projects

Number Title Start Funding scheme
183550 Real time Exploration of GTPase-Cytoskeletal feedback underlying Contractile Actomyosin Systems 01.09.2019 Sinergia

Abstract

The cytoskeleton present in nearly all living cells is a network of linear polymers. It plays an essential role in vital cellular processes like division or migration and determines the mechanical properties of many cell types. The main components of the cytoskeleton are the proteins actin and tubulin, which assemble into actin filaments and microtubules, respectively. They interact with numerous proteins, notably molecular motors that convert chemical energy into mechanical work. From a physical point of view, the cytoskeleton belongs to the class of active matter, where energy is fed into the system at the level of its constituents. Physical studies of active gels have revealed phenomena that are unknown to equilibrium polymer networks. For example, active gels can spontaneously generate flows or topological point defects. Most theoretical studies of active gels have focused on static geometries. Moving or dividing cells, however, change their shapes due to cytoskeletal activity. We propose to study the interplay between the dynamics of active gels and of the domains they are confined to. We propose to use phase-field methods to account for changes in the domain shapes. Phase fields have successfully been used in studies of phase separation, crystallization, viscous fingering, fracture dynamics, etc. Recently, phase-field methods have also been introduced to study the dynamics of cellular shapes, notably in the context of cell migration. We plan to employ this tool to study three different topics. First, we want to continue our exploration of the role of spontaneous actin waves for cell motility. Second, we plan to study instabilities of the actin cortex -- a thin actin layer below the outer membrane of animal cells -- in particular in the context of cell division. Third, we want to apply these techniques to study blebs that appear, when cell membrane detaches from the actin network and bulges. We will solve the corresponding dynamic equations numerically on GPUs. Analytical work will be carried out in the sharp interface limit.We expect our studies to significantly advance our understanding of cellular shape regulation and to reveal further interesting phenomena unique to active matter. The techniques we will develop for the description and analysis of our systems will be useful also in other contexts, notably for investigating morphogenetic processes during embryonic development. In the context of cell migration, we expect to obtain new insights into behavioral consequences of actin-wave driven motility. Our studies on cell division should allow us to assess the role of dynamic instabilities for furrow formation and cell cleavage. The project part on blebs will be used to verify current conceptions about bleb formation and retraction.
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