Nanopatterning for control of cell cytoskeleton

NU 2018-027

INVENTORS

Chad Mirkin*

Milan Mrksich*

Brian Meckes

Maria Cabezas

SHORT DESCRIPTION

Polymer pen lithography (PPL) to spatially define locations where cells can adhere to a substrate in aniosotropic patterns.

BACKGROUND

Cells have unique shapes that play significant roles in their function; cell shape influences cellular processes including survival, migration, and differentiation. Nano- and micro-patterning approaches have been used to control this shape, and therefore function, by chemically defining interactions between cells and surfaces at the level of the actin fiber cytoskeleton. While refined control of actin fibers around the periphery of a cell has been achieved, actin fibers at the sub-cellular level remain largely uncontrolled. Achieving high-throughput, high-resolution control over the actin cytoskeleton can enhance desired cell outcomes and create a more homogeneous cell population for cell-based assays.

ABSTRACT

Northwestern researchers have utilized cantilever-free scanning probe lithographic techniques, termed polymer-pen lithography (PPL), to spatially define specific locations where cells can interact with a substrate to form a focal adhesion, a specific interaction that couples the actin cytoskeleton to the surrounding environment. In this work, PPL is used to pattern self-assembled monolayers of alkanethiolates on gold that present fibronectin and control the shape and sizes of single cells in culture. Arranging the focal adhesions yields organized and contractile actin cytoskeleton oriented in a desired direction. This increased control over the actin cytoskeleton allows for better control over cell differentiation (e.g., adipogenic vs. osteogenic fate) and enhances the uniformity of the cells on a substrate. This work demonstrates a programmable approach that arbitrary ECM pattern arrangements, including aniosotropic cues, can be easily explored to modulate cytoskeletal organization and control stem cell fate.

APPLICATIONS

Modulation of actin fiber orientation to direct cytoskeleton organization.
Differentiation of stem cells to specific targeted lineages for tissue engineering.
Research tools for cell-based screening for drug discovery.

ADVANTAGES