Spatiotemporal patterning of photoresponsive DNA-based hydrogels to tune local cell responses

Abstract

Understanding the spatiotemporal effects of surface topographies and modulated stiffness and anisotropic stresses of hydrogels on cell growth remains a biophysical challenge. Here we introduce the photolithographic patterning or two-photon laser scanning confocal microscopy patterning of a series of o-nitrobenzylphosphate ester nucleic acid-based polyacrylamide hydrogel films generating periodically-spaced circular patterned domains surrounded by continuous hydrogel matrices. The patterning processes lead to guided modulated stiffness differences between the patterned domains and the surrounding hydrogel matrices, and to the selective functionalization of sub-regions of the films with nucleic acid anchoring tethers. HeLa cells are deposited on the circularly-shaped domains functionalized with the MUC-1 aptamers. Initiation of the hybridization chain reaction by nucleic acid tethers associated with the continuous hydrogel matrix results in stress-induced ordered orthogonal shape-changes on the patterned domains, leading to ordered shapes of cell aggregates bound to the patterns.

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

“… 6 – 8 As well, high cross-linking density also favors dense structure and enhanced stiffness. It is worth noting that the fabrication approaches (in situ gelation, 9 electrospinning, 10 micropatterning, 11 3D bioprinting, 12 microfluidics, 13 etc. ), also matter for hydrogel properties and determine their applications.…”

Photoswitchable architecture transformation of a DNA-hybrid assembly at the microscopic and macroscopic scale

“…Hydrogels that exhibit memory properties of their permanent shape attract considerable attention and are subject of various studies. Upon application of a stimulus, such as pressure, 24,74 light, 27,29,75 etc., they undergo transitions into a metastable structure. 72,73,76,77 Applying a counter stimulus, the original permanent shape can be recovered due to a memory code present in the gel.…”

“…Hydrogels that exhibit memory properties of their permanent shape attract considerable attention and are subject of various studies. Upon application of a stimulus, such as pressure, 24,74 light, 27,29,75 etc. , they undergo transitions into a metastable structure.…”

“…Due to these unique properties, DNA is particularly versatile in controlling assembly and organization as seen in DNA-based nanotechnology, 4,[6][7][8][9][10][11][12][13][14][15] DNA-origami, 8,16-21 hydrogels, [22][23][24][25] and polymeric materials as a crosslinker. [26][27][28][29] Alternatively, a singlestranded DNA (ssDNA) can be employed as a readily available and programmable template to construct supramolecular DNA hybrid structures. 2 This concept of molecular recognition-driven self-assembly was established by Lehn et al and can be used in a bottom-up approach to easily obtain complex architectures from simple building blocks.…”

Printing and Erasing of DNA‐Based Photoresists Inside Synthetic Cells

“…[ 37 ] In another study, photoresponsive DNA strands were used as cross‐links for polyacrylamide hydrogels, enabling the specific patterning of the resulting hydrogels. [ 38 ] Moreover, DNA hydrogels offer versatile opportunities due to their programmability and stimuli‐response. [ 25,26 ]…”