Biology subjects

Peng, Y.-H.

Publications and source records attributed to Peng, Y.-H..

4 recordsLinked to original sources

bioRxiv2026

Mapping 3D cellular mechanical activity with matrix-embedded DNA force-history probes

Cells continuously integrate mechanical cues from the surrounding extracellular matrix to control fundamental biological processes such as proliferation and migration. Yet, studying the mechanical activity of cells in 3D over time is challenging, low-throughput, and requires specialized equipment. Here, we introduce DNA-based force-history probes, which convert transient pico-Newton forces into cumulative fluorescent signals within a mechanically adjustable DNA-crosslinked cell culture matrix. The probes provide control over signal lifetimes, allowing stress patterns to be recorded over minutes to days with tunable temporal memory. We use this system to visualize the mechanical activity of breast cancer spheroids and map the trajectories of migrating cancer cells. By combining different fluorophores and DNA-encoded signal lifetimes, we produce dual-color probes that associate temporal information to mechanical events. Overall, force-history probes provide an endpoint-readable record of mechanical cell-matrix activity, offering new opportunities for studying cell function in physiology and disease.

bioengineering↗

bioRxiv2025

LASSO: versatile and selective biomolecule pulldown with combinatorial DNA-crosslinked polymers

Current methods for sequence-selective biomolecule isolation suffer from high cost, off-target effects, and limited flexibility. Here, we introduce LASSO (crossLink-Assisted Sequence-Selective isOlation), a versatile platform using programmable polymer phase separation to capture biomolecules under native conditions. LASSO relies on combinatorial crosslinker libraries--diverse mixtures of DNA strands that collectively trigger the formation of highly swollen polymer agglomerates with near-zero background binding. We demonstrate >80% pulldown efficiency for diverse targets, including DNA, SARS-CoV-2 RNA, and human thrombin. LASSO provides 8-20x higher binding capacity (4 nmol/mg polymer) than commercial microbeads. In RNA-seq workflows, LASSO depleted ribosomal RNA with 86% efficiency while yielding up to 7x fewer off-target outliers (p<0.001) versus state-of-the-art magnetic beads (riboPOOLs) and RNase H (NEBNext) kits. Thrombin was captured via switchable aptamers with 92% efficiency, and a gentle release mechanism allowed the subsequent isolation of 72% enzymatically active proteins from the polymer. LASSOs cost-effectiveness ($0.96/sample vs. $46-$51 for commercial kits), long-term stability (7+ years), simple usage, and modularity position it to transform diagnostics, transcriptomics, and bionanotechnology workflows.

bioengineering↗

bioRxiv2024

Assembling a true "Olympic Gel" from >16,000 combinatorial DNA rings

Olympic gels are an elusive form of soft matter, comprising a three-dimensional network of mechanically interlocked cyclic molecules. In the absence of defined network junctions, the high conformational freedom of the molecules was previously theorized to confer unique mechanical properties to Olympic gels, such as non-linear elasticity and unconventional swelling characteristics. However, the synthesis of an Olympic gel exhibiting these intriguing features is challenging, since unintended crosslinking and polymerization processes are often favored over cyclization. Here, we report the successful assembly of a true Olympic gel from a library of DNA rings comprising more than 16,000 distinct molecules. Each of these rings contains a unique sequence domain that can be enzymatically activated to produce reactive termini that favor intramolecular cyclization. We characterized the genetic, mechanical, and structural characteristics of the material by next-generation sequencing, oscillatory rheology, large-scale computational simulations, atomic force microscopy, and cryogenic electron microscopy. Our results confirm the formation of a stable Olympic gel, which exhibits unique swelling behavior and an elastic response that is exclusively determined by entanglements, yet persists on long time scales. By combining concepts from polymer physics, synthetic biology, and DNA nanotechnology, this new material class provides a flexible experimental platform for future studies into the effects of network topology on macroscopic material properties and its function as a carrier of genetic information in biological and biomimetic systems. This work moreover demonstrates that exotic material properties can emerge in systems with a high compositional complexity that is more reminiscent of biological than synthetic matter.

bioengineering↗

bioRxiv2022

Dynamic matrices with DNA-encoded viscoelasticity for advanced cell and organoid culture

3D cell and organoid cultures, which allow in vitro studies of organogenesis and carcinogenesis, rely on the mechanical support of viscoelastic matrices. However, commonly used matrix materials lack rational design and control over key cell-instructive properties. Herein, we report a class of fully synthetic hydrogels based on novel DNA libraries that self-assemble with ultra-high molecular weight polymers, forming a dynamic DNA-crosslinked matrix (DyNAtrix). DyNAtrix enables, for the first time, computationally predictable, systematic, and independent control over critical viscoelasticity parameters by merely changing DNA sequence information without affecting the compositional features of the system. This approach enables: (1) thermodynamic and kinetic control over network formation; (2) adjustable heat-activation for the homogeneous embedding of mammalian cells; and (3) dynamic tuning of stress relaxation times over several orders of magnitude, recapitulating the mechanical characteristics of living tissues. DyNAtrix is self-healing, printable, exhibits high stability, cyto-and hemocompatibility, and controllable degradation. DyNAtrix-based 3D cultures of human mesenchymal stromal cells, pluripotent stem cells, canine kidney cysts, and human placental organoids exhibit high viability (on par or superior to reference matrices), proliferation, and morphogenesis over several days to weeks. DyNAtrix thus represents a programmable and versatile precision matrix, paving the way for advanced approaches to biomechanics, biophysics, and tissue engineering. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/510936v2_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1a9c486org.highwire.dtl.DTLVardef@a578d7org.highwire.dtl.DTLVardef@1a08f7dorg.highwire.dtl.DTLVardef@2c64af_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗