Biology subjects

Solorio, L.

Publications and source records attributed to Solorio, L..

5 recordsLinked to original sources

bioRxiv2026

Coupling fibroblast mechanotransduction signaling to tissue growth in a multiscale model of skin expansion

Skin growth and remodeling underlies health, disease, and treatments such as tissue expansion (TE). The mechanotransduction pathways in dermal fibroblasts are increasingly well characterized, and tissue-level growth has been described phenomenologically, but coupling between cell-level signaling and tissue-level growth remains poorly understood. We develop a dermal fibroblast signaling network through extensive literature data curation, comprising 151 reactions among 96 nodes. The inputs are mechanical stretch and eight ligands (TGF{beta}, PDGF, FGF, IL1, IL6, TNF, AngII, ET1); outputs of interest span ECM-enzymes (proMMP1/2/9, MMP1/2/9), ECM proteins (CImRNA, collagen I, fibronectin), and fibroblast activity (SMA, proliferation). Implemented as a logic-based ODE system, the network reproduces 82% of the calibration dataset and agrees with independent validation data. Sensitivity analysis reveals a tension-dependent regulation of signaling: at baseline tension, outputs are governed by many boosters (nodes that positively influence downstream targets) and one dominant brake, LATS1/2, whereas at high tension control consolidates and new, tension-specific regulators such as integrin (ITGB1) emerge. Multiple pathway axes converge on a few central regulators, producing pronounced crosstalk, most notably between TGF{beta} and mechanical tension. Finally, linking the collagen outputs to a tissue-level growth formulation yields a bidirectional mechanical-biochemical coupling that reproduces tension-induced skin growth measured in a porcine TE model. This framework establishes a comprehensively calibrated dermal fibroblast signaling network coupled to tissue-level growth, opening opportunities for targeted TE interventions.

biophysics↗

bioRxiv2024

Rheological and Lipid Characterization of Minipig and Human Skin Tissue: A Comparative Study Across Different Locations and Depths

Understanding the rheology of minipig and human skin is crucial for enhancing drug delivery methods, particularly for injections. Despite many studies on skins viscoelasticity, especially the subcutaneous layer, comparative analyses across different clinical sites are scarce, as is data on the impact of hydration or lipid levels. This study employs shear rheology and lipid analysis to evaluate viscoelasticity and lipid content across three anatomical locations --breast, belly, and neck and three different depth layers in Yucatan minipigs. It reports on how viscoelastic properties change with frequency, time, and strain, noting strain-stiffening and shear-thinning at high strain amplitudes. Human male and female abdominal tissues are also compared to minipig tissues, highlighting distinct viscoelastic traits and lipids role in them. The findings suggest the existence of species, anatomical location, tissue depth, and sex-based rheological differences. We also concluded the minipig male tissue is a more accurate model for human male subcutaneous tissue than for females.

biophysics↗

bioRxiv2023

KRAS-mediated upregulation of CIP2A promotes suppression of PP2A-B56α to initiate pancreatic cancer development

Oncogenic mutations in KRAS are present in approximately 95% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) and are considered the initiating event of pancreatic intraepithelial neoplasia (PanIN) precursor lesions. While it is well established that KRAS mutations drive the activation of oncogenic kinase cascades during pancreatic oncogenesis, the effects of oncogenic KRAS signaling on regulation of phosphatases during this process is not fully appreciated. Protein Phosphatase 2A (PP2A) has been implicated in suppressing KRAS-driven cellular transformation. However, low PP2A activity is observed in PDAC cells compared to non-transformed cells, suggesting that suppression of PP2A activity is an important step in the overall development of PDAC. In the current study, we demonstrate that KRASG12D induces the expression of both an endogenous inhibitor of PP2A activity, Cancerous Inhibitor of PP2A (CIP2A), and the PP2A substrate, c-MYC. Consistent with these findings, KRASG12D sequestered the specific PP2A subunit responsible for c-MYC degradation, B56, away from the active PP2A holoenzyme in a CIP2A-dependent manner. During PDAC initiation in vivo, knockout of B56 promoted KRASG12D tumorigenesis by accelerating acinar-to-ductal metaplasia (ADM) and the formation of PanIN lesions. The process of ADM was attenuated ex vivo in response to pharmacological re-activation of PP2A utilizing direct small molecule activators of PP2A (SMAPs). Together, our results suggest that suppression of PP2A-B56 through KRAS signaling can promote the MYC-driven initiation of pancreatic tumorigenesis.

cancer biology↗

bioRxiv2020

A Tumbling Magnetic Microrobot System for Biomedical Applications

A microrobot system comprised of an untethered tumbling magnetic microrobot, a two degree of freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High frequency ultrasound imaging allows for real-time determination of the microrobots position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a one hour time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobots constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot systems capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.

bioengineering↗

bioRxiv2019

Transglutaminase-2 facilitates extracellular vesicle-mediated establishment of the metastatic niche

AbstractThe ability of breast cancer cells to interconvert between epithelial and mesenchymal states contributes to their metastatic potential. As opposed to cell autonomous effects, the impact of epithelial-mesenchymal plasticity (EMP) on primary and metastatic tumor microenvironments remains poorly characterized. Herein we utilize global gene expression analyses to characterize a metastatic model of EMP as compared to their non-metastatic counterparts. Using this approach we demonstrate that upregulation of the extracellular matrix crosslinking enzyme tissue transglutaminase-2 (TGM2) is part of novel gene signature that only emerges in metastatic cells that have undergone induction and reversion of epithelial-mesenchymal transition (EMT). Consistent with our model system patient survival is diminished when primary tumors demonstrate enhanced levels of TGM2 in conjunction with its substrate, fibronectin. Targeted depletion of TGM2 inhibits metastasis, while overexpression of TGM2 is sufficient to enhance this process. In addition to being present within cells, we demonstrate a robust increase in the amount of TGM2 and crosslinked fibronectin present within extracellular vesicle (EV) fractions derived from metastatic breast cancer cells. Confocal microscopy of these EVs suggests that FN becomes fibrillated on their surface via a TGM2 and Tesin1-dependent process. Upon in vivo administration, the ability of tumor-derived EVs to induce metastatic niche formation and enhance subsequent pulmonary tumor growth requires the presence and activity of TGM2. Finally, we develop a novel 3D model of the metastatic niche to demonstrate that education of pulmonary fibroblasts via pretreatment with tumor-derived EVs promotes subsequent growth of breast cancer cells in a TGM2-dependent fashion. Overall, our studies illustrate a novel mechanism through which EMP contributes to metastatic niche development and distant metastasis via tumor-derived EVs containing abberent levels of TGM2 and fibular FN.

cancer biology↗