Membrane biophysics

I very recently completed a PhD with Mike Evans. As detailed on my science page we were working on model colloidal systems to study some general features of phase transitions (gas-liquid, crystal-fluid, etc.) particularly in polydisperse substances — where every particle is slightly different to every other. The work produced some interesting results and nice publications with more to come, and culminated in this hefty tome.

I’ll now be staying at Leeds for the next couple of years, but my day-to-day work (i.e. funding) concerns a new topic: the biophysics of lipid membranes. Yes, having spent over 3 years figuring out how to explain to people what I do, I now have to start from scratch. It seems like a good time for a quick post explaining the topic, and what attracted me to it.

Cells and life

How did life begin? Of course, nobody knows precisely. However, we can speculate reasonably on what the earliest life was like. It is overwhelmingly likely that the first things in any sense ‘alive’ were tiny protobacterial cells, roughly spherical containers of stuff with little internal structure which, agonisingly slowly, acquired the capabilities we associate with life: reacting to their environment, duplicating themselves, and so on. A nice paper by a collaborator of mine discusses (Section 2.1) the characteristics of the first life, and reasons why the simplest — earliest — possible life probably must have inhabited the length scale we associate with simple bacteria.

One of the criteria for life is particularly simple and, to me, quite satisfying, because it seems to spring from simple logic rather than particular accidental features of our world. A living thing in the sense we understand it should have a boundary which distinguishes it from its environment. Where does the outside end and the organism begin? The other criteria for life — reproduction, motility, response to environment etc. etc. — rely on there being an answer to this question. Intimately related to this is the idea that something living should be able, to any extent, to regulate its internal chemistry, distinct from changes in its environment. If we, humans, simply filled with seawater when entering the ocean; or if our organs were not contained ‘inside us’ but just wandered around the universe independently, we’d have a hard time proving ourselves to be alive. Similarly, the cell’s boundary couldn’t just be a fully permeable, abstract dividing line which allowed the cell interior to remain in permanent, passive equilibrium with the outside world. So, cells specifically and life generally must be able to selectively exchange chemicals with the outside world. Hopefully, my point is coming into view. A cell boundary is key to life not just as a logical prerequisite for even speaking about life as we know it, but as the focal point for the very processes that render the cell alive: its interactions with its environment.

Lipid membranes

In living cells, ‘lipid membranes’ serve to encase the cell and to mediate exchange with the environment. What are they? For a physicist, a lipid is most instructively thought of as being a tadpole-like molecule. The ‘head’ likes water — it is hydrophilic, because it is polar and therefore doesn’t too much disrupt water’s hydrogen-bonding network — while the ‘tails’ don’t like water, being nonpolar and therefore hydrophobic for the same reason that everyday oils are. Allowing a whole bunch of these lipids to undergo thermal motion in a watery solvent results in arrangements which keep the water-hating tails as far as possible from the water, shielded by the heads. See this picture. The lipid bilayer arrangement is a roughly flat sheet which can fold up to make a roughly spherical vesicle (i.e. a structure appropriate to form a cell).

The lipid membrane mediates a huge variety of vital processes: cell division requires the spherical membrane to form a ‘bud’ which eventually breaks off; selective exchange of ions and other important things takes place through ion-channel proteins embedded in the membrane; inter-cell signalling and detection processes necessarily take place through the membrane; the list goes on.

Understanding how lipid bilayers work involves a heavy physics component, to understand properties such as membrane curvature, asymmetry (one layer being different from the other), phase separation, formation and break-up, and the interdependence of these properties. The CAPITALS programme is a large collaborative project aimed at this target, and my new work is part of it. The people in charge (principal investigators) are real experts in the field, and everyone involved is extremely switched-on and open-minded — it’s great to be part of it.

Here’s a snapshot from some early computer simulation work I’ve been doing. It’s a homemade version of a wide class of models where simplified lipids are represented as chains of 3 beads, one hydrophilic (green) one and two hydrophobic (red) ones.



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