Pr Francesco PIAZZA
UNIVERSITE D'ORLEANS, UFR Faculte des Sciences
Département de Physique et Sciences de l'Ingénieur
Laboratoire : CBM-CNRS UPR 4301 du CNRS.
In all biochemical reactions occurring in living tissues, reactants have to form an encounter complex before the specific chemical step. Invariably, in order to reach their binding partners, biomolecules have to diffuse in complex environments, both very crowded with all sorts of other biomolecules and organelles and confining, due to the presence of different membranes and cytoskeletal structures that strongly compartmentalize the available space.
Under such conditions, the standard Smoluchowski theory for biomolecular encounters valid in ideal solutions is no longer applicable and the need emerges for more sophisticated theoretical paradigms accounting explcitly for crowding and confinement in the computation of encounter rates.
In this talk, I will illustrate a general theoretical paradigm that we are developing in our group to solve this problem. Using addition theorems for spherical harmonics, we compute the diffusion rate to a sink in the presence of crowding agents/obstacles that we model by assemblying spheres of arbitrary radius and endowed with arbitrary reactivity, from fully reflecting (purely excluded volume) to fully absorbing (competitive binding partners). We consider both diffusion in an unbounded domain and diffusion occurring within a spherical domain, as an attempt to model encounters occurring within a cell. Different applications will be discussed, such as diffusion to a binding pocket in a coarse-grained model of protein and reactions occurring in vesicles and other kinds of man-made nanoreactors.