BIOMIMESYS: BIOlogical Material to Investigate Morphological changes by Engineering bioinspired SYStems

Biological cells generate forces that drive various functions, including intracellular processes such as division and transport, as well as responses to extracellular stimuli such as cell polarization and migration. These processes are accomplished via structural changes in the cytoskeleton resulting in cell shape changes. The forces behind these deformations originate from interactions between cytoskeletal components, namely biopolymers and motor-proteins. Mechanical stimulation from the extracellular environment also influence these interactions, leading to remodelling of cellular morphology. Thus, the cytoskeleton is an adaptive and active material, which uses chemical energy at the nanoscale giving rise to active behaviour at cellular length scale. Currently, interactions between individual cytoskeletal biopolymer and motor-proteins at the nanoscale are relatively well-known. However, experimental characterization of the forces that these components collectively generate and how they can shape cells remains a significant challenge blocking fundamental progress in biology and innovation in materials science. The aim of this research is to understand how the evolution of cellular forces within the intracellular space, from the molecular length scale to the entire cell, leads to changes in cell structure and regulation of morphology. This will be achieved by developing an innovative experimental platform to tackle these fundamental questions. I will engineer a 3D system made of biopolymers and motor-proteins able to mimic the functionality of the cytoskeleton. This bioinspired experimental setup allows us to investigate in a controlled manner how living matter respond to mechanical external stimuli at different length scales and accomplish shape changes. I will employ microfluidics, photo-switchable proteins, and fluorescence microscopy to achieve the following objectives: Understanding the effects of geometry on the self-organisation of 3D bioinspired systems and how the external environment couples with the active network activity. How? By assembling active networks made of microtubules and motor-proteins and enclose them within confinements of varying nature and size, from compartments with solid walls to vesicles with deformable membranes. Unravelling activity at different length scales (from few microtubules and motor-proteins to the interconnected network) and studying how this activity is transferred across these length scales. How? By integrating photo-switchable motor-proteins to locally activate by light defined portions of the active networks. Studying the mechanisms of how cellular active networks collectively change their symmetric morphology to a tapered shape, aka symmetry-breaking. How? By encapsulating and anchoring active networks within cell-like membranes, and locally triggering network activity using light. The proposed project has interdisciplinary scope with relevance for scientists interested in understanding the physics of life. In the UK the growing interest in this topic led to the foundation of the scientific network Physics of Life, which includes researchers in physical and biological sciences. The successful assembly of these active self-organising structures would be a significant milestone for novel model systems that will enable us to understand the physical forces in the cytoskeleton. By considering the collective forces generated by biopolymers and motor-proteins involved in cellular processes, we can unlock new investigation avenues into cellular diseases. Processes such as metastasis and wound healing are based on force generation at different length scales and cellular deformation leading to migration. The new insights offered by this proposal may lead to novel medical research that address physical forces for the development of new therapeutic procedures.