Biology subjects

Bennewitz, R.

Publications and source records attributed to Bennewitz, R..

4 recordsLinked to original sources

bioRxiv2026

Data-driven predictive design of engineered living hydrogels

Engineered living materials (ELMs) offer a promising route to biologically manufactured materials for healthcare, construction and manufacturing. However, their rational design is limited by the lack of quantitative relationships linking design parameters to material properties. Here, we show that a tabular foundation model (TabPFN), informed by a small library of living hydrogels, accurately predicts macroscopic material properties from genetic and process parameters. Models were evaluated for predicting storage modulus (G'), fibre content, thickness, and permeability of Escherichia coli-produced living hydrogels containing CsgA-based fibres fused to genetically encoded PEG-like biopolymers. On an independent validation set, TabPFN achieved the strongest prediction for G' (R2 = 85.1%), reducing RMSE by 48.0% compared to linear regression. Property-guided design further enabled identification of parameters for achieving living hydrogels with desired properties. These results establish a broadly applicable framework for predictive design of ELMs, reducing experimental screening and accelerating the discovery of materials with targeted properties.

synthetic biology↗

bioRxiv2024

Bacterial Engineered Living Materials modulate Mechanosignaling in Mammalian Cells

Engineered living materials (ELMs) are gaining momentum for biomedical applications as self-replenishing drug depots, smart wound dressings, or as wearable sensors. Current studies on ELM-host interaction are mainly limited to the exchange of biochemical cues between ELMs and surrounding cells and tissues. Here we show that the genetically programmed mechanical properties of ELMs modulate mechanosignaling pathways in mammalian cells cultivated onto the living materials. To this aim, we genetically modulated curli fiber production in E. coli and analyzed the impact on the mechanical properties of the resulting ELMs. The living materials were used as matrix for the cultivation of mammalian cells engineered with a fluorescent reporter to indicate the activation of the mechano-responsive Hippo signaling pathway. We demonstrate that different genetically programmed ELM compositions translated into differential regulation of mechanosignaling in mammalian cells. These findings provide the perspective of using ELMs as extracellular matrix with genetically programmable mechanics for mammalian cells while also highlighting the need to consider the mechanical properties of therapeutic ELMs when assessing interaction with surrounding tissues. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/620857v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@1a1ef9borg.highwire.dtl.DTLVardef@79c49forg.highwire.dtl.DTLVardef@5bb04dorg.highwire.dtl.DTLVardef@193a808_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOToC figureC_FLOATNO C_FIG

bioengineering↗

bioRxiv2020

Optoregulated force application to cellular receptors using molecular motors

Mechanotransduction events in physiological environments are difficult to investigate, in part due to the lack of experimental tools to apply forces to mechanosensitive receptors remotely. Inspired by cellular mechanisms for force application (i.e. motor proteins pulling on cytoskeletal fibers), here we present a unique molecular machine that can apply forces at cell-matrix and cell-cell junctions using light as an energy source. The key actuator is a light-driven rotatory molecular motor linked to polymer chains, which is intercalated between a membrane receptor and an engineered biointerface. The light-driven actuation of the molecular motor is converted in mechanical twisting of the polymer chains, which will in turn effectively "pulls" on engaged cell membrane receptors (integrins, cadherins...) within the illuminated area. Applied forces have the adequate magnitude and occur at time scales within the relevant ranges for mechanotransduction at cell-friendly exposure conditions, as demonstrated in forcedependent focal adhesion maturation and T cell activation experiments. Our results reveal the potential of nanomotors for the manipulation of living cells at the molecular scale and demonstrate, for the first time, a functionality which at the moment cannot be achieved by any other means.

cell biology↗

bioRxiv2019

Targeted demethylation of H3K9me3 and H3K36me3 improves somatic cell reprogramming into cloned preimplantation but not postimplantation bovine concepti

Correct reprogramming of epigenetic marks in the donor nuclei is a prerequisite for successful cloning by somatic cell transfer. In several mammalian species, repressive histone (H) lysine (K) trimethylation (me3) marks, in particular H3K9me3, form a major barrier to somatic cell reprogramming into pluripotency and totipotency. We engineered bovine embryonic fibroblasts for the doxycycline-inducible expression of Kdm4b, a demethylase that removes histone 3 lysine 9 trimethylation (H3K9me3) and H3K36me3 marks. Upon inducing Kdm4b, H3K9me3 and H3K36me3 levels reduced [~]3-fold and [~]5-fold, respectively, compared to non-induced controls. Donor cell quiescence has been previously associated with reduced somatic trimethylation levels and increased cloning efficiency in cattle. Simultaneously inducing Kdm4b expression (via doxycycline) and quiescence (via serum starvation), further reduced global H3K9me3 and H3K36me3 levels by a total of 18-fold and 35-fold, respectively, compared to non-induced, non-starved control fibroblasts. Following somatic cell transfer, Kdm4b-BEF fibroblasts reprogrammed significantly better into cloned blastocysts than non-induced donor cells. However, detrimethylated donors and sustained Kdm4b-induction during embryo culture did not increase rates of post-blastocyst development from implantation to survival into adulthood. In summary, KDM4B only improved somatic cell reprogramming into early preimplantation stages, highlighting the need for alternative experimental approaches to reliably improve somatic cloning efficiency in cattle.

developmental biology↗