Initial landmark studies in the design of synthetic hydrogels for intestinal organoid culture identified precise matrix requirements for differentiation, namely decompression of matrix-imposed forces and supplementation of laminin. But beyond stating the necessity of laminin, organoid-laminin interactions have gone largely unstudied, as this ubiquitous requirement of exogenous laminin hinders investigation. In this work, we exploit a fast stress relaxing, boronate ester based synthetic hydrogel for the culture of intestinal organoids, and fortuitously discover that unlike all other synthetic hydrogels to date, laminin does not need to be supplemented for crypt formation.
View Article and Find Full Text PDFThe cell nucleus is continuously exposed to external signals, of both chemical and mechanical nature. To ensure proper cellular response, cells need to regulate not only the transmission of these signals, but also their timing and duration. Such timescale regulation is well described for fluctuating chemical signals, but if and how it applies to mechanical signals reaching the nucleus is still unknown.
View Article and Find Full Text PDFThis study describes the synthesis of novel amphiphilic linear-dendritic block copolymers and their self-assembly in water to form supramolecular nanoreactors capable of catalyzing Suzuki-Miyaura coupling reactions under "green" conditions. The block copolymers were formed through copper(I)-catalyzed alkyne-azide cycloaddition between azide functionalized poly(benzyl ether) dendrons as the perfectly branched blocks, as well as bis-alkyne modified poly(ethylene glycol), PEG, as the linear block. A first-generation poly(benzyl ether) dendron (G1) was coupled to a bis-alkyne modified PEG with molecular mass of 5 kDa, forming an ABA copolymer (G1)-PEG5k-(G1) (yield 62%), while a second-generation dendron (G2) was coupled to a 11 kDa bis-alkyne modified PEG to produce (G2)-PEG11k-(G2) (yield 49%).
View Article and Find Full Text PDFStiffness and forces are two fundamental quantities essential to living cells and tissues. However, it has been a challenge to quantify both 3D traction forces and stiffness (or modulus) using the same probe in vivo. Here, we describe an approach that overcomes this challenge by creating a magnetic microrobot probe with controllable functionality.
View Article and Find Full Text PDFSpatiotemporally coordinated transformations in epithelial curvature are necessary to generate crypt-villus structures during intestinal development. However, the temporal regulation of mechanotransduction pathways that drive crypt morphogenesis remains understudied. Intestinal organoids have proven useful to study crypt morphogenesis in vitro, yet the reliance on static culture scaffolds limits the ability to assess the temporal effects of changing curvature.
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