Dr Cristiano De Michele

Nationality: 
Italy
Programme: 
Smart Loire Valley Programme*
Period: 
December, 2015 to November, 2016

From : “Sapienza” University of Rome

Project

“Cell biology from the colloid physics perspective: a computational study of biomolecular interactions mid-way between the test-tube and the cell”

CBM-CNRS 

Host scientist

Pr Francesco PIAZZA

Summary of the project

The cell interior is an amazingly complex and crowded medium. Up to 40 % of its available volume is swarming with hundreds of thousands of biomolecules of all type and size, highly structured in specific compartments separated by different membranes and filled up with small organelles and a tight web of cytoskeletal structures. How proteins can possibly manage to find their unique binding partners in such an environment of mind-bogging complexity, looking more as a bustling city than a dull biological background, is still one of the most elusive puzzles in science.

   Thanks to the most recent technical advances in imaging and single-particle tracking techniques, paralleled by tremendous progress in computational approaches, it is now generally believed that the environment itself is a key factor in shaping the biochemical processes that it hosts. However, it is very difficult to interpret experiments on biomolecular transport and association performed in living cells, due to the plethora of unknown and spurious effects that are likely to affect the measurements, arising from all the processes running in parallel to the one under scrutiny and most probably intertwined with it in unknown ways. The common solution to these strongly impeding disadvantages is the test tube. However, in order to perform experiments under the required conditions, one pays the price of studying a pale copy of the process of interest, distilled to such dilute and controlled conditions to  become with great probability an utterly different process.
   The present project aims at taking an intermediate step from the test-tube to the cell stopping half-way, in the realm of colloids. With the help of the research fellow, and drawing on concepts and methods from the physics of colloids, we will build computational tools to simulate biomolecular association in complex environments. Biomolecules will be modeled as hard convex objects (HCO) or collections of freely hinged HCOs. The environment will be replenished of crowding agents of different shape (shape matters), size (exploring the effect of specific mixes) and concentration (crowding). Enthalpic interactions will be allowed for through sticky spots (local piece-wise constant potentials), thus enabling us to explore crowding effects on biomolecular association along the brim of subtle enthalpy/entropy trade-offs.