Optothermally Responsive Nanocomposite Generating Mechanical Forces for Cells Enabled by Few-Walled Carbon Nanotubes

Abstract

We have designed and fabricated a nanocomposite substrate that can deliver spatially and temporally defined mechanical forces onto cells. This nanocomposite substrate comprises a 1.5-mm-thick near-infrared (NIR) mechanoresponsive bottom layer of few-walled carbon nanotubes (FWCNTs) that are uniformly distributed and covalently connected to thermally responsive poly(N-isopropylacrylamide) and an approximately 0.15-mm-thick cell-seeding top layer of collagen-functionalized poly(acrylic acid)-co-poly(N-isopropylacrylamide) that interpenetrates into the bottom layer. Covalent coupling of all the components and uniform distribution of FWCNTs lead to a large local mechanoresponse. As an example, 50% change in strain at the point of irradiation on the order of 0.05 Hz can be produced reversibly under NIR stimulation with 0.02 wt % FWCNTs. We have further demonstrated that the mechanical strain imposed by NIR stimulation can be transmitted onto cells. Human fetal hepatocytes change shape with no sign of detrimental effect on cell viability. To the best of our knowledge, this is the first demonstration of a nanocomposite platform that can generate fast and controlled mechanical force to actuate cells. Since the amplitude, location, and timing of force can be controlled remotely with NIR, the nanocomposite substrate offers the potential to provide accurately designed force sequences for tissue engineering.

Photothermally triggered actuation of hybrid materials as a new platform for in vitro cell manipulation

“…5a,b). Uniaxial strain is a highly relevant strain profile for studies in cell mechanotransduction132627, and the ability to uniaxially and repeatedly displace some points on the surface at user-defined locations and times is not possible with other active cell culture materials3031323334. Flexible membrane devices such as the Flexercell can be operated at higher frequencies (up to 10 Hz), but there is no option of only activating a small area on the membrane111213262728.…”

“…However, with the HAIRS- x NR material this type of stimulus can be limited down to a fraction of a single cell, which facilitates the study of how these types of forces propagate inside of cells and cause changes16. No other active material enables the directional distortion of selected cells at such a small scale and with such high degrees of cell strain3031323334.…”

“…They have exploited the properties of shape-memory polymers (SMPs)3031, magnetic particles dispersed in soft deformable matrix materials3233, and temperature-sensitive and reversible volume-changing hydrogels such as poly(N-isopropylacrylamide) (PNIPAAm)3435. However, none have reached the goal of generating rapid and directional surface reconfiguration and cell deformation in sub-cellular sized regions of the surface that are not pre-determined during the fabrication process3031323334. In addition, while the magnetic particle-based materials and thermo-responsive polymer materials do allow highly localized surface deformations, the forces generated have been limited to the nN and pN range3235.…”

“…1). The photothermally driven volume reduction of the PNIPAAm-NP combination has proven useful for previous biomedical applications, as the relatively low LCST of PNIPAAm signifies that the operational temperature range of the system is safe, and both the polymer and NPs are known to be biocompatible3447484950. On the basis of type of incorporated NP, HAIRS platform could be designed to selectively respond to light wavelengths in different regions of the spectrum51.…”

Aptamer-Functionalized Hydrogel for Self-Programmed Protein Release via Sequential Photoreaction and Hybridization

“…1–8 These materials have been widely used in drug delivery, cell biology, molecular machine, information technology, and so on. 9–15 Using responsive materials to control protein release is one of the most intriguing potential applications, 16–17 since a lot of proteins, particularly cytokines and growth factors, can cause severe side effects when delivered systematically.…”