Molecular Dynamics Simulation of the Extracellular Matrix

During metastasis, a cancer cell invades the extracellular matrix (ECM) by secreting an enzyme that cleaves collagen molecules. A better understanding at the molecular level of the elastic behavior of the ECM will provide significant insight into the mechanisms involved in cell migration, cell adhesion and during cell communication. We model the ECM in a molecular dynamics simulation using LAMMPS, Large-scale Atomic/Molecular Massively Parallel Simulator. Since collagen is the most abundant protein in the ECM, we create an environment containing collagen and water molecules at a density equivalent to the composition of the Matrigel^TM ECM samples used in our experiments. We deform the simulation box to calculate the stress tensor and elastic constants of the system. We mimic the enzymatic effect on the ECM by cleaving a peptide bond in the collagen molecules and recalculating the elastic constant. The results are compared to the experimental results which show the elastic constant decreases as more collagen molecules are scissioned by the enzyme. The findings will provide molecular-level insight to interpret measurements made at the cellular level.