Squishy Matter and Active Chemistry: Understanding Membrane Organization

TURNING POINTS

Squishy matter and active chemistry: understanding membrane organization

Satyajit Mayor

I had just established my laboratory at the the day. However, I found myself at odds with the GPI-anchor of the major variant surface National Centre for Biological Sciences (NCBS) the dominant preoccupations in my academic glycoprotein (VSG) is assembled. The rationale in Bangalore, and was recovering from the environment and yearned to study biology. I was noble: understanding the chemistry of this inevitable stress, when a very cheerful character began taking almost every course and elective specific attachment mechanism and identifying dropped into my office. He asked if I would be offered that could provide a whiff of anything a ‘chemical’ that could poison it to render the able to explain the properties of cell membranes biological; I even equated chemistry with biol- parasite defenceless and rid the world of sleep- to him, as he was a physicist from the neigh- ogy and immersed myself in the lore of physical ing sickness. Within a year, the GPI-anchor had bouring Raman Research Institute, and had just and organic chemistry, equilibrium thermody- been discovered in almost all eukaryotic systems moved from Madras to explore the scientific namics and chemical kinetics. For my under- as a general, alternative mechanism of perma- environs of Bangalore and to see if there were graduate thesis, I joined the laboratory of (the nently anchoring proteins to membranes. I had any biologists who knew anything about cell late) Dr Anil Lala, an enthusiastic bioorganic learnt an important lesson: nothing in biology membranes. Just as I began to get rid of him, say- chemist who was developing photoactivatable is either simple or unique. The biology of any ing that the chemistry of the cell membrane was probes to study how proteins could insert into organism is a consequence of evolution and complex enough and I did not understand very membranes. However, when I finally arrived survival — something that a chemical system much about the physical properties of cell mem- in a pure biology laboratory for my doctorate simply does not even have to consider. branes, he threw a squishy jelly-like object that at the Rockefeller University, I found it deeply For my postdoctoral work with Fredrick looked like a lizard at the ceiling. To our amaze- intellectually disorienting: there seemed to be Maxfield, I elected to study how GPI- ment, it stuck there and refused to come down. more to the story than a chemist’s view of bio- anchored proteins behave in their own special Until then I had been quite unaware of the whole logical systems as assemblages of molecules milieu — the membrane — which I have subse- field of squishy (soft condensed) matter and if I subject to laws so neatly laid out in physical quently discovered requires deep understand- had known it existed, I would have imagined that and organic chemistry textbooks. ing of local lipid dynamics and composition in it would help in the development of face creams Extraordinary things were being discov- the living cell. Back in India, I set up my own and toothpaste. I certainly knew nothing about ered in biological systems that violated all the laboratory, focusing on GPI-anchored protein the huge strides made in this field in exploring chemistry I had learnt: for example in Gunter organization in time and space in living cells, ‘active’ systems, situated away from equilib- Blobel’s laboratory the world’s most complex which I believe may lead us to discover a new rium. While we waited for the lizard to detach, nano-machine — the ribosome — was busy not chemical language that cells use to regulate their a conversation ensued between Madan Rao and only making proteins but also engaging with local molecular environment. myself, which has led to an exciting dialogue that the translocation machinery as a gatekeeper Although the jury is still out, the special has lasted many years. And one that has been a of protein secretion. How could systems as chemistry and physics of ‘squishy matter’ may turning point in my attempts to understand the complex as these ever work or be understood? be key to understanding the mechanism under- connection between the chemistry of biomol- I decided to stick to simpler biochemistry that I lying how cells create such crazy molecular ecules and their behaviour in living cells. might hope to understand. (I would ask authors assemblies — even if they are made of the same When I was an undergraduate, I went to to make cuts here done) ‘chemicals’ as artificial membranes. The squishy an engineering school, the Indian Institute of I joined the laboratory of George Cross. At lizard proved to be the beginning of a rich col- Technology (IIT, Bombay), and found myself the time his laboratory had discovered the struc- laboration with Madan Rao, to explore how in the positivist world of engineering solutions ture of a strange glycolipid whose only apparent active processes that maintain systems far from where heat transfer efficiencies and an under- function was to keep the protective surface coat equilibrium can create cellular structures and standing of fluid mechanics were the order of protein of the trypanosome parasite attached regulate composition in living cell membranes. to the membrane. With Anant Menon, a bio- Satyajit Mayor is at the National Centre for Biological Sciences, Bellary Road, Bangalore 560005, India. physicist from Cornell, I embarked on a ‘simple’ COMPETING FINANCIAL INTERESTS e-mail: [email protected] (bio)chemical expedition to understand how The authors declare no competing financial interests.