Cell Migration
Adhesion modulates cell morphology and migration within dense fibrous networks
Understanding cell migration in complex media is a challenging subject
Biology
Biochemistry
Physics
Mathematics
Computational science
multidisciplinary effort
Computational Modelling
Two different models for describing cell migration in fibres
Dissipative Particle Dynamics (DPD)
Phase-Field Model (PFM)
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Continuum model
Rigid Fibres
Cell described as a set of monomers
Flexible fibres
Complementary approaches
How the mechanical constraints imposed by the extracellular matrix (ECM) affect migration?
Parameters we varied
adhesiveness
density of fibres
and we measured
shape deformity
surface roughness
cell velocity
Pore cross section
Results
DPD
PFM
velocity x pore cross-section
comparing with experimental data
RT Medium
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RT GM6001
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experimental cells present more plasticity
enabling migration through smaller pores with higher velocity
MMP inhibitor GM6001 affects cell migration decreasing velocity
which brings the experimental results closer to ours
GM6001 suppresses the MMP enzyme family
for a long time MMP was only associated with ECM degradation and remodelling
but in recent years were found strong evidences of a broader action
MMP
migration
survival
adhesion
degradation
remodelling
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the velocity dependency as a function of the adhesiveness for PFM and DPD compared to in vitro experiments with fibronectin coating
we found a non-monotonic behaviour, similar to observed in vitro
a maximum in velocity indicates an optimal adhesion for migration
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this is related to an increase in cell deformity
we measured the roughness of the cell surface
it increases considerable for densities $\rho$ higher than 0.5 and adhesivity $eta$ higher than 0.9
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another measure of shape deformity is the radius of gyration $R_g$
it shows that the maximum in velocity is related to a maximum in cell deformation
what would happen with velocity as a function of pore cross-section if we increase adhesion?
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when we increase adhesivity from 0.0 to 0.5 our results for small pores become similar to the experimental data with MMP inhibitor
increasing even more adhesivity to 1.0 the model is able to reproduce the experimental results without the inhibitor
our hypothesis is that the inhibitor is affecting cell adhesion meaningfully
since our model reproduces the two experimental conditions by only varying adhesivity
being the effect observed in velocity due to a decrease in adhesion and not necessarily a consequence of suppressing ECM degradation
For more details, please read our preprint:
Further enquiries: mms@uc.pt
https://www.biorxiv.org/content/10.1101/838995v1
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