Shrink Wrapping Cells in a Defined Extracellular Matrix to Modulate the Chemo-Mechanical Microenvironment

Area of Science:

• Biomaterials Engineering
• Cell Biology
• Tissue Engineering

Background:

• Cell-matrix interactions are crucial for tissue integration and mechanosensitive signaling.
• Current *in vitro* models using adsorbed extracellular matrix (ECM) proteins fail to replicate native basement membranes.
• This limitation hinders the study of cell adhesion to specialized ECM structures like those found in cardiomyocytes and endothelial cells.

Purpose of the Study:

• To develop an engineered biomaterial that recapitulates the native ECM niche for improved *in vitro* cell studies.
• To create a functional and instructive matrix for single cells and small cell ensembles.
• To overcome limitations of current cell encapsulation technologies.

Main Methods:

• Developed a surface-initiated assembly process to engineer ECM proteins into nanostructured sheets.
• Engineered ECM sheets were shrink-wrapped around cells, mimicking native basal lamina density and thickness.
• Utilized fibronectin, laminin, fibrinogen, and collagen type IV for tailored structure and composition.

Main Results:

• High cell viability was observed for various cell types, including C2C12 myoblasts, bovine corneal endothelial cells, and cardiomyocytes, after the shrink-wrapping process.
• The engineered ECM significantly modulated cytoskeletal structure and the stability of cell-matrix adhesions.
• Demonstrated distinct effects on cell behavior in both 2D and 3D microenvironments compared to non-encapsulated controls.

Conclusions:

• The engineered ECM sheets provide a functional and instructive matrix niche that closely mimics native tissue environments.
• This novel approach enhances the study of cell-matrix interactions *in vitro*.
• The technology offers a promising platform for advanced cell culture and tissue engineering applications.