PROJECT SUMMARY
Cells are dynamic, multiscale materials. Their ability to sense and respond to a wide variety of stimuli is
predicated on the hierarchical construction of the actin cytoskeleton, where individual actin monomers assemble
to form filaments, which themselves assemble to form more complicated structures. Therefore, to engineer nano-
bio interfaces that can stimulate a specific cellular response, we propose to test a biomimetic approach, where
our designer material will exhibit hierarchy and function across the same length scales as the cytoskeleton. This
project aims to engineer arrays of spiky gold nanoparticles with spike characteristics that are commensurate with
actin filaments and where the particle-particle spacing corresponds to the size of mature focal adhesions. Our
fabrication method is biocompatible, high-resolution, and high-throughput. We will investigate the physical effects
of topographical features across length scales as well as chemical effects. Since the smallest feature size of the
spiky nanoparticles (the tips) have radii of curvature tunable in the 5-10 nm range, we can test whether known
nanotopographical sensing pathways occur at length scales similar in size to single proteins as well as the effects
on cell phenotype resulting from reduced focal adhesion density. We will evaluate for synergistic effects between
nano- and microscale topographical sensing on contact guidance of the cytoskeleton by comparing responses
from different spike and nanoparticle array geometries.
As a model problem, we aim to manipulate the process of macropinocytosis. While nanoscale curvature is
known to promote clathrin-mediated endocytosis, the effects of curvature on macropinocytosis remain unclear.
By varying the spike features of the nanoparticles and the DNA-aptamer functionalization of their surfaces, we
will test for synergy between two factors: (1) enhanced rates of macropinocytosis via receptor binding to the DNA
ligands; and (2) effects of priming the cell membrane for macropinocytosis through nanotopographical curvature.
We expect that our biomimetic approach enabled by spiky nanoparticle arrays will have a significant impact on
a range of questions in biotechnology, from fundamental mechanisms for early-stage endocytosis to applications
such as biofouling-resistant sensors and the use of topographical cues as mechanobiological stimuli.