Ultraflexible Nanowire Array for Label- and Distortion-Free Cellular Force Tracking

Abstract

Living cells interact with their immediate environment by exerting mechanical forces, which regulate important cell functions. Elucidation of such force patterns yields deep insights into the physics of life. Here we present a top-down nanostructured, ultraflexible nanowire array biosensor capable of probing cell-induced forces. Its universal building block, an inverted conical semiconductor nanowire, greatly enhances both the functionality and the sensitivity of the device. In contrast to existing cellular force sensing architectures, microscopy is performed on the nanowire heads while cells deflecting the nanowires are confined within the array. This separation between the optical path and the cells under investigation excludes optical distortions caused by cell-induced refraction, which can give rise to feigned displacements on the 100 nm scale. The undistorted nanowire displacements are converted into cellular forces via the nanowire spring constant. The resulting distortion-free cellular force transducer realizes a high-resolution and label-free biosenor based on optical microscopy. Its performance is demonstrated in a proof-of-principle experiment with living Dictyostelium discoideum cells migrating through the nanowire array. Cell-induced forces are probed with a resolution of 50 piconewton, while the most flexible nanowires promise to enter the 100 femtonewton realm.

High‐Aspect‐Ratio Nanostructured Surfaces as Biological Metamaterials

“…C) Individual nanowire deflection as a function of time, with corresponding calculated force (where possible to estimate), illustrating the ability to monitor dynamic changes in force. A–C) Adapted with permission . Copyright 2019, American Chemical Society.…”

“…Nanowires, [136,137] nanopillars, [31] nanostructures, [138,139] nanopits/nanopores, [140,141] nanoelectrodes, [28,65,85,142] ≈0.04-0.5 [143] ≤300 (in theory, but in reality individual field size ≈1 × 1) [144] Best resolution Flexible design (no fixed tooling required)…”

“…[426,427] Deformation of the surface by adherent cells, and knowledge of the material's mechanical properties, allows the applied force to be determined. Motivations include developing biomechanical sensors that can be used to directly spatially map the magnitude of forces exerted by cells on their environment, [136] but avoiding the mechanical coupling between sensing sites that convolutes 2D traction force measurements. [428]…”

“…[430] Recently, Paulitschke et al have presented gallium arsenide nanowires to measure the cellular forces exhibited by amoeba (Dictyostelium discoideum). [136] They used inverted conical nanowires which are thinner at the base than the tip, which the authors argue facilitates very small spring-constants and hence high sensitivity, while the large smooth head reflects incident light and enables the nanowire deflection to be readily imaged (Figure 27). Other approaches have incorporated plasmonicactive gold nanoparticles into the tips of polymer micropillars for optical readout, [25] or used AFM to directly probe nanowire deflection.…”

“…A-C) Adapted with permission. [136] Copyright 2019, American Chemical Society. nanostructured surfaces provide a valuable tool for exploring the single-cell origins of biofilm formation.…”