Download All cellular organisms sense and respond to mechanical forces, in

All cellular organisms sense and respond to mechanical forces, in order to survive against extreme
environmental conditions, of which osmotic pressure is the most ancient and universal. Rapid drop in
external osmolarity leads to several atmospheres increase of internal pressure, posing life-threatening
conditions. Without a protective mechanism against such extremes, cell lysis becomes inevitable,
resulting for instance, in bacteria bursting after rain. Ion channel pore proteins embedded within the cell
membrane have evolved in such a way that they can be directly opened by bilayer stretching, to relieve
intracellular pressure and prevent cell lysis.
Mechanosensitive (MS) channels are also present in eukaryotes and are central in pain reception, touch,
hearing and cardiovascular architecture. Recently, it was shown that mechanosensation is not limited
to MS but also regulates potassium and other types of eukaryotic channels. Therefore, this fundamental
biophysical property seems to constitute a universal mechanism for ion channel regulation.
We are currently developing a multidisciplinary approach spanning from biochemistry (cysteine
modification) and structural biology (x-ray crystallography) to biophysics (EPR spectroscopy and
single molecule electrophysiology) in order to structurally and functionally characterise novel ion
channels, known to mechanosense. Through this process we could identify common structural patterns
linked to mechanosensitivity and elucidate at a molecular detail the transition from the open to closed
state and vice versa (a process also known as gating), of these systems. Further exploitation of the latter
would lead to the development of novel chemical and physical tools for the manipulation of membrane
pores for medical and nano-technological purposes.