Abstract:
:A filopodium is a cytoplasmic projection, exquisitely built and regulated, which extends from the leading edge of the migrating cell, exploring the cell's neighborhood. Commonly, filopodia grow and retract after their initiation, exhibiting rich dynamical behaviors. We model the growth of a filopodium based on a stochastic description which incorporates mechanical, physical, and biochemical components. Our model provides a full stochastic treatment of the actin monomer diffusion and polymerization of each individual actin filament under stress of the fluctuating membrane. We investigated the length distribution of individual filaments in a growing filopodium and studied how it depends on various physical parameters. The distribution of filament lengths turned out to be narrow, which we explained by the negative feedback created by the membrane load and monomeric G-actin gradient. We also discovered that filopodial growth is strongly diminished upon increasing retrograde flow, suggesting that regulating the retrograde flow rate would be a highly efficient way to control filopodial extension dynamics. The filopodial length increases as the membrane fluctuations decrease, which we attributed to the unequal loading of the membrane force among individual filaments, which, in turn, results in larger average polymerization rates. We also observed significant diffusional noise of G-actin monomers, which leads to smaller G-actin flux along the filopodial tube compared with the prediction using the diffusion equation. Overall, partial cancellation of these two fluctuation effects allows a simple mean field model to rationalize most of our simulation results. However, fast fluctuations significantly renormalize the mean field model parameters. The biological significance of our filopodial model and avenues for future development are also discussed.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Lan Y,Papoian GAdoi
10.1529/biophysj.107.123778subject
Has Abstractpub_date
2008-05-15 00:00:00pages
3839-52issue
10eissn
0006-3495issn
1542-0086pii
S0006-3495(08)70386-2journal_volume
94pub_type
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