(217bc) Covalent Attachment of Polyelectrolyte Multilayers to Cells

Biohybrid materials integrate synthetic materials with biological systems in order to confer unique properties to existing biological functions. This class of materials can be used in a variety of applications, such as sensing, drug delivery, or biological imaging. One type of biohybrid material is the cell backpack, which incorporates polyelectrolyte multilayer (PEM) patches with cells. Various cargoes, such as small molecules, nanoparticles, or labeling moieties, can be incorporated into the backpacks for cells to carry, making cellular backpacks a versatile platform for drug delivery. These PEM backpacks are fabricated through a combination of photolithography and layer-by-layer (LbL) assembly. The backpacks are hundreds of nanometers thick, a few microns wide, and attach to part of the cell surface.

The original cell adhesive PEMs produced in our group contained hyaluronic acid paired with chitosan, since CD44 receptors on lymphocyte surfaces bind to hyaluronic acid. However, this receptor-ligand binding interaction is not strong and is specific to certain types of cells, so more robust and versatile techniques for cell attachment need to be developed, such as covalent attachment. This would not only create an irreversible chemical bond between the backpack and the cell, but it would also allow the backpacks to attach to a greater variety of cell types.

Covalent attachment can be achieved by introducing functional groups into the polymers of the cell adhesive multilayers, which would react with proteins on the cell surface. One target functional group includes the maleimide group, which reacts with thiols present on cysteine residues of proteins. Maleimide groups are grafted onto poly(allylamine hydrochloride) using a heterobifunctional cross-linker, sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC). The functionalized polymer is then paired with poly(acrylic acid) for LbL assembly. The cellular backpacks are then reacted with lymphocytes for the covalent attachment reaction. The cells are incubated with both an array of backpacks attached to a glass substrate as well as releasable backpacks that react with cells in solution. In addition to incorporation into cell backpacks, polymers that covalently attach to cell surfaces can also be used to create other types of biohybrid materials for a variety of applications. The development of polymers that covalently attach to cells could thus open a broad area of new ideas to explore.