This is essentially what is now called mechanobiology and mechanobiology is actually a field of, if you wish, cell biology which studies the force generated by cells and how cells respond to this force, how cells sense the forces. So I’m particularly studying the cytoskeleton, the system of fibular structures that are involved in the generation of force and how this system is associated with cell adhesion to the extracellular matrix because, as we have shown quite some time ago, focal adhesions are actually the cell matrix adhesion mediated by integrin receptors are the devices that cells use to measure the forces that are actually applied by contractile systems. So, in fact, using focal adhesions a cell obtains information about the mechanical characteristics of the microenvironment which is critically important for the organisation of cell migration and for establishing contacts between neighbouring cells and finally, of course, for remodelling of the extracellular matrix. So cross talk between adhesion and the cytoskeleton is the main subject of what we are doing.
Are transcription factors involved in this process or is it purely mechanical?
It is definitely, as everything, the cell has a global regulation based on regulation of transcription and so on but the cell has also an instant system of regulation, a signalling system, which responds to immediate external signals by a kind of activation of contractility by remodelling of the cytoskeleton of the cell. This is essentially a system related to small G proteins and this is also in the field of our interest.
What is the link between diseases and cancer in particular?
Since, as far as I understand, you’re more interested in cancer, what are the cancer cells? What is the major feature of cancer cells is an inability to arrange to build proper tissue architecture. As a consequence cancer cells are free from all the constraints that a normal cell has and tend to invade other tissues and to metastasise and so on. All these defects, in fact, are defects that are related to the kind of wrong behaviour of the cytoskeleton and cell adhesion. So, generally speaking, almost everything that we are studying is definitely related to cancer because every kind of interaction between, say, the cytoskeleton and adhesion which we are learning from the behaviour of normal cells are suspicious in terms that it may change the behaviour of cancer cells. We are trying not to lose this opportunity.
What are the potential applications?
This is not our immediate field but, in fact, it is maybe the best example of definite importance of cytoskeletal studies in cancer is the simple fact that one of the most important and promising anti-cancer drugs, like Taxol, has a specific target in the cytoskeleton - it affects microtubule stability. The same is true for several other typical anti-cancer drugs so the search for compounds that affect the cytoskeleton and related cell compartments is very promising in cancer treatment, I believe.
Could you tell us more about your research?
Yes, we are essentially interested, as I said, in the cross talk between the cytoskeleton and cell adhesions. What we are studying is how cells really organise the cytoskeleton upon attachment to the proper extracellular matrix. The organisation of actin cytoskeleton is very complex, there are several compounds like different kinds of protrusions, but also there is a system of special contractile bundles of actin filaments that are directly connected to junctions to contact cells with the extracellular matrix. This system, first of all, is very beautiful but of course it is important for maintenance of cell shape and then for cell migration. We are studying how such systems are organised actually from scratch when the cell is attaching to the substrate. We have some interesting findings related to that, the latest one is that self-organisation of this system has an obvious kind of chirality which helps cells to distinguish between left and right. So cells are really more clever than we thought before and they can not only just migrate but they can distinguish between the direction of migration. This is a consequence of specific features of the actin cytoskeleton. This is what we are doing just now.
What are the future scenarios?
Definitely we should understand better the mechanisms of focal adhesion mechanosensitivity which we discovered several years ago and still it is a hotspot in the studies of the cell behaviour. This is the general avenue, the interactions between the cytoskeleton and adhesions and how it helps cells to sense the physical characteristics of the microenvironment. This will be our direction for several years I believe.
