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Details of Grant 

EPSRC Reference: EP/V043498/1
Title: Bio-inspired active sheets: control of membrane shape dynamics by force-generating biopolymer networks
Principal Investigator: Koester, Dr DV
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Delft University of Technology
Department: Warwick Medical School
Organisation: University of Warwick
Scheme: New Investigator Award
Starts: 01 July 2022 Ends: 30 June 2025 Value (£): 597,117
EPSRC Research Topic Classifications:
EPSRC Industrial Sector Classifications:
Pharmaceuticals and Biotechnology
Related Grants:
Panel History:
Panel DatePanel NameOutcome
08 Sep 2021 EPSRC Physical Sciences September 2021 Announced
Summary on Grant Application Form
The overall aim of this project is to develop an experimental system and a theoretical framework of bio-inspired active sheets that undergo controlled shape changes based on self-organisation of force generating biopolymers. The composite nature of the surface of mammalian cells, basically a lipid bilayer linked to an active actomyosin network, constitutes an exquisite example of an active sheet, that is robust and can take various geometries. Despite many research efforts, the underlying physical mechanisms by which actomyosin dynamics generate defined membrane shapes remain poorly understood. This problem combines hydrodynamics of the fluid lipid membrane with the mechanics of active polymer networks where effects on multiple length scales play a role.

Using a bottom-up approach we decorate giant unilamellar vesicles (GUVs) with thin networks of actin filaments and myosin motors and study how network activity and reorganisation drives membrane shape deformations at different length scales. By combining this with cutting edge 3D lattice light sheet microscopy (LLSM), quantitative image analysis and theory we want to test our hypothesis that the composition of thin, force generating actomyosin gels determines how lipid membranes adopt specific morphologies (tubes, ellipsoid, dumbbell). In addition, we plan to study the role of asymmetrical myosin distribution on GUV deformations by using micropipette assisted protein deposition. Using micropipette aspiration, we will address the role of membrane tension on shape changes in actomyosin decorated GUVs. Throughout the project, we will develop and test a theoretical model of such bio-inspired active sheets. The close back and forth communication between experimental and theoretical work will ensure an efficient planning of experiments and will accelerate the project overall.

A better theoretical and experimental grasp of the actomyosin-lipid membrane composite will be of high interest in the fields of biophysics, soft condensed matter, and engineering. This project will inform the design of active, controllable, and biocompatible carriers, will uncover basic principles governing cell shape control and will strengthen the capabilities of the UK science community in reconstituted, cell-like systems.

Key Findings
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Organisation Website: http://www.warwick.ac.uk