Molecular Playground/MMP14

From Proteopedia

One of the CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground. Molecular Playground banner: " MMP-14 allows for 3D in vitro cell migration"

Structure

Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) is 1 of ~24 members of the MMP family of endopeptidases. MMPs are zinc dependent proteinases that are capable of degrading virtually any extracellular matrix component [1]. Inherently, this enables MMPs to be a key player in regulation of cell behavior. There are 8 structure classes for MMPs and of these classes, 5 are secreted molecules and 3 are membrane-type [2]. MT1-MMP or also known as MMP-14 is covalently linked to the cell membrane.

More information on MMPs can be found on proteopedia at MMP.

Inhibition

Tissue inhibitors of metalloproteinases (TIMPs) are small molecules that can regulate the activity of MMPs. is capable of binding the of MMP-14, creating a new cell surface involved in the activation of MMP-2 [3].

Extracellular Matrix Components

MMP-14 degrades the following substrates in the extracellular matrix [2]:

Aggrecan

Collagen I

Collagen II

Collagen III

Entactin/Nidogen

Fibrillin

Fibronectin

Gelatin I

Laminin

Vitronectin

α2-M

α1-PI

Factor XII

Fibrin

Fibrinogen

ProMMP2

ProTNFα

My Research Interest

In the Peyton Lab I work to combine materials science with stem cell and cancer biology to design in vitro model biomaterial systems to understand cell motility. My project aims to design 3D biomaterial tissue mimics using poly(ethylene glycol). I incorporate degradable MMP crosslinkers into these biomaterials to allow cells the opportunity to move throughout the matrix and remodel their surrounding microenvironment.

References

[1] L. Coussens, et al., Matrix Metalloproteinase Inhibitors and Cancer: Trials and Tribulations, Science, 2002. 295: p. 2387-92

[2] M. Sternlicht, et al., How Matrix Metalloproteinases Regulate Cell Behavior, Annu Rev Cell Dev Biol, 2001. 17: p. 463–516.

[3] Egeblad, et. al., New Functions for the Matrix Metalloproteinases in Cancer Progression, Nat. Rev. Can., 2002, 2: 162-74