Mechanotransduction in membranes

Optical imaging of electrical and mechanical properties of cell membranes

Every living cell in the human body is enclosed by a membrane that protects the content from unwanted contamination whilst at the same time, allowing specific molecules to pass in and out of the cell. The membrane also acts as an electrical insulator and a voltage is maintained across the membrane. This voltage is vital to many cellular functions and it is believed that a failure in these electrical properties is linked to major diseases, including diabetes, cardiovascular diseases and cancer.

A detailed understanding of the fundamental physics associated with the electrical and mechanical properties of the membrane is vital if the complex biochemical processes occurring in the cell are to be revealed. The cell membrane is neither solid nor liquid but comprises of a double layer of lipid molecules forming a liquid crystal phase. A liquid crystal is generally formed from long, rod-shaped molecules which tend to align in the same direction, but have no positional order. Liquid crystals have unique physical and optical properties which have found applications in many devices such as high-tech optical displays found in flat-screen televisions, computer monitors and mobile phones. This study applies theories and methodologies previously developed through the study of these synthetic systems to cell membranes to explore the links between liquid crystalline properties and the physiology of mammalian cells.

The Flexoelectric effect

The specific phenomenon investigated in this work is known as the flexoelectric effect, in which the deformation of a layer of polar molecules generates a measurable electrical polarisation. It is postulated that the flexoelectric effect plays a crucial role in fundamental physiological processes, influencing the distribution of proteins within the membrane and the transport of specific ions in and out of the cell and even acting as a method of converting physical stimulae to chemical signals and vice versa. The ability of the cell to measure and respond to mechanical and fluid mechanical signals such as those arising from the flow of blood over the surface of cells lining the walls of blood vessels is crucial in normal growth and development and many diseases are linked to failure of this mechanism. However, the precise signalling mechanisms are unclear and a better understanding would transform our understanding of disease processes and may lead to new methods of treatment.

Techniques

Optical imaging techniques developed in the multiphoton laboratory are used to uncover the basic physical principles involved in these processes. Systems such as vesicles formed from mammalian lipids to the more complex membrane of the red-blood cell can be explored using Coherent Anti-Stokes Raman Scattering (CARS). This novel technique uses light to detect the spatial distribution and orientation of specific chemical bonds such as the carbon-hydrogen bonds of the lipid molecules. These highly detailed 3-D images of the distribution and orientation of the lipids etc. in the cell membrane are produced with a sub-micron resolution. This structural information can be combined with a 3-D "map" of the electrical charge distribution in the membrane by incorporating novel dyes into the layers which are sensitive to changes in their local electrical environment. This allows the effects of various mechanical and shear stresses, as well as variations in the properties of the host environment to be explored. Questions such as how the natural bending of the cell membrane affects the alignment of the lipids, inducing flexoelectric polarisation are currently being addressed with the intention of ultimately exploring how this influences the behaviour of proteins and the transport of ions through the cell membrane.