Project Details
Description
PROJECT SUMMARY
We propose to develop a novel computational platform, called TRACTOR, to couple theoretical
models of cell motility and cell-matrix interaction with a sophisticated model of matrix mechanics
and reorganization. TRACTOR will address a significant technology gap by providing a link
between cell mechanics and matrix mechanics, both of which have been studied extensively but
whose synergistic interplay remains largely unexplored. For this proof-of-concept study, the
matrix will be represented as a network of type I collagen fibers, as in commonly-used collagen
gel assays, modeled as a semiflexible string of beads connected by harmonic bonds. The action
of the cell will be modeled by introducing a separate set of isolated beads - called "tractors" -
that (1) extend from the cell, (2) attach to nearby collagen fibers, (3) retract back to the cell,
dragging the collagen with them, and (4) release the collagen. A critical element of the process
is that after the third step, collagen beads that have been brought into close contact by the
action of the tractors will form new bonds, creating the plasticity reported by multiple
researchers in collagen mechanics. The new bond formation introduces irreversibility to the
process, so the matrix released in step (4) does not return to its pre-step-(1) configuration. As
the cycle repeats, the cell will be able to induce large deformations of the matrix even though
each individual tractor generates relatively small amounts of motion. A key feature of the
TRACTOR platform, to be developed during this initial study but implemented only in its
simplest form for exploratory purposes, will be its flexibility to accommodate different models of
cell mechanics and matrix mechanics and composition. TRACTOR will also be computationally
innovative, leveraging the open-source LAMMPS software's energy minimization functionality;
this functionality, normally used as a prelude to molecular dynamics calculations, will be
repurposed to provide an efficient, flexible base for TRACTOR and for long-term distribution of
the TRACTOR code to other users. Key proof-of-concept milestones proposed herein are
based on well-established experimental observations: (1) a working TRACTOR model of a cell
compacting the matrix around it, (2) a working TRACTOR model of a cell polarizing and exerting
anisotropic traction in an anisotropic collagen gel, and (3) a working TRACTOR model of
multiple cells interacting mechanically within a collagen gel. Achievement of these milestones
will demonstrate the potential of the TRACTOR framework and justify further pursuit of it as a
modeling tool for theoretical studies of cell-matrix interaction.
Status | Active |
---|---|
Effective start/end date | 9/22/22 → 8/31/24 |
Funding
- National Institute of General Medical Sciences: $222,652.00
- National Institute of General Medical Sciences: $184,625.00
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