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Séminaire de Francesco PIAZZA

Macromolecular crowding effects in collagen fibrillogenesis

Francesco PIAZZA


Macromolecular crowding effects in collagen fibrillogenesis

The competition for access to space that arises among macromolecules in dense and confining
environments is the basis of the macromolecular crowding phenomenon, known to modulate biochemical
reactions in subtle fashions. Crowding is an optimized physiological condition in metazoans,
and originates from a mixture of heterogeneous biomolecules, organelles and cytoskeletal structures,
which occupy up to 40 % of the available space in and around cells.

In this study, we investigated the kinetics of collagen fibrillogenesis in solutions crowded
with homogenous and heterogenous (mixtures of) artificial crowding agents.
As a general finding, we show that crowding speeds up both the kinetics of nucleation and the
elongation of mature fibrils. Moreover, we demonstrate that a synergistic effect
is created by a mixture of two different populations of artificial crowders, providing small
crowders with extra volume occupancy when in the vicinity of larger crowders.

Dwelling on a recently introduced theory of diffusion-limited encounters in crowded media
based on concepts from the physics of colloids, we provide some theoretical rationale for our results.
In particular, we describe the physiological mechanism by which synergistic effects maximize volume
exclusion with the minimum amount of heterogeneous crowders, demonstrating how evolutionarily optimized
crowded conditions found in vivo can be reproduced for biotechnological applications in vitro.