Mechanics of the cell interface

The physical coat of biological cells- a thin fluid lipid membrane, supported on a deformable actin network, is remarkable in its ability to adapt and respond to mechanical stretch. The properties of the coat allow cells to sustain the transient dilation of lungs, intestines, bladder, etc., to squeeze through small capillaries, and they are what we currently lack in the design of microcapsules for delivery and release.

Previous work by us and others on reconstituted systems and on living cells lead us to suggest that the mechanical competence of the cellular coat emerges from the material properties of the lipid membrane and the actin cortex, as well as from their coordinated structural remodeling upon mechanical deformation. In particular we propose that upon stretch the actin cortex stiffens and protects the lipid membrane from rupturing, and upon compression, the cortex fluidizes and allows the membrane to reshape and regulate its excess area.

To be able to verify these mechanisms and to reveal processes that are inaccessible by whole cell experiments, we will assemble the cellular coat onto an elastic substrate and image the structural remodeling of the membrane and the actin cortex during stretch and compression. With this project we aim to 1) build the experimental setup, 2) elucidate the ability of the cellular coat to sustain mechanical deformation by passive restructuring, and 3) establish complementary collaborative work with labs working on cell and tissue mechanics. This project will prepare the grounds for our future studies on the ability of cells to actively adapt and respond to mechanical deformation, which links among others to processes such as morphogenesis, embryogenesis, or migration of cancer cells.

In addition, during and after the project, we will collaborate with an industrial partner to translate our findings on the mechanics of the cellular coat to the design of stimuli-responsive capsules for flavour release and delivery.

Economic impact
Biological systems are not only able to sustain a wide range of mechanical perturbations, but can also actively adapt and respond to them. Understanding the design principles behind such desirable mechanical properties will facilitate the development of more efficient and sustainable materials and technologies. The UK is traditionally strong in formulation design and this project will further contribute to the strengthening of this sector.
Lipid bilayers are a preferred material for bio-delivery systems, sensors, and coatings due to their biocompatibility, selective permeability, and ability to self-assemble. Currently there are about 15 marketed lipo-based drug delivery systems, and many more in clinical trials. A major drawback is their mechanical fragility and irreversible opening. The current project offers a fresh approach to lipid bilayer technologies. It takes advantage of the emergent properties a lipid bilayer coupled to a deformable polymer matrix. Stimuli-induced deformations of the matrix result in reversible pore opening and formation of lipid protrusions, which can be utilized in the design of mechano-responsive lipid technologies for controlled release and delivery.
Understanding the ability of the cell interface to adapt to mechanical perturbations by structural reorganizations- an objective of the current project- will facilitate the design of adaptive materials that can restructure and change their properties locally in response to non-uniform loading. Examples of such materials may include textiles, coatings, shoe soles, etc. that soften non-uniformly in response to the pressure applied by the individual wearer and could be used for preventing pressure ulcers.

Societal impact
At this early stage it is difficult to predict the societal impacts of the proposed research. However we expect that advancing the knowledge of the role of mechanical forces in physiology, disease and aging will lead to more efficient medical treatment/prevention methods and healthier society. Furthermore, the concepts of "emergence" and "bio-inspired design and technologies" considered in this project are popular topics in the public domain that provide opportunities to attract the interest of the public and engage it in the research process.

People
The interdisciplinary nature of the project and the planned collaborative work with biologists, engineers and industry provide opportunities for wide exposure and interdisciplinary training of the researchers. For example, the appointed postdoctoral researcher, Dr. Kirby, will have the opportunity to apply his skills in optics and instrumentation and will gain valuable, transferable skills and knowledge in completely new research areas, such as biophysics and soft matter, providing further opportunities in these rapidly developing subjects. He will be involved in the supervision of PhD and undergraduate students, and will interact closely with the academic and industrial partners on the project, forming useful ties for potential future collaborations and meeting several formal criteria for his personal career advancement. The PhD student, co-supervised jointly with Mondelez, will have the opportunity to train in translating fundamental research to application-driven technologies, preparing them to become the future research-led innovators. Some of the project tasks will be given as projects to undergraduate students with biological or physical backgrounds, thus training them in collaborative work. Moreover, the PI who is a lecturer the Centre for Doctoral Training in Soft Matter and Interfaces at Durham, will use the interdisciplinary practices of the project to inform her teaching in soft matter, biomaterials, and in responsible research and innovation.
Finally, we expect that our project will be of interest to artists and designers, willing to explore together with us the concepts of emergence, active matter and biomimetic design into their work.