Biology subjects

Barriga, E. H.

Publications and source records attributed to Barriga, E. H..

6 recordsLinked to original sources

bioRxiv2026

Computational insights on the competition between electrotaxis and durotaxis

Understanding how cells migrate in response to external cues has important implications for biology, medicine, and bioengineering. Chemical, mechanical, and electrical signals are the primary drivers of directed cell migration, and each has been extensively studied over the past decades. Among them, chemical cues were the first to be investigated and remain the most widely studied due to their undeniable role in in vivo guidance. Mechanical signals--particularly substrate stiffness gradients--have gained prominence for their ubiquity across cell types and their potential to direct migration. More recently, growing evidence suggests that electrotaxis offers a highly precise and programmable means to guide cell movement. Despite this, these cues are often studied in isolation, whereas in vivo they typically coexist and interact. Using wellestablished biophysical models, we investigate how mechanical and electrical signals cooperate and how they can be engineered to compete for control over cell migration. We demonstrate that an electric field can override and even reverse durotaxis, with outcomes that depend strongly on the specific cell type. To address this large variability in controlling cell migration, we propose particular steps toward further exploration. To support such future research, we provide a freely available platform for predicting electro-mechanical interactions in cell migration, based on a given cells sensing and signaling characteristics, which could tailor the mechanical and electrical signals that arise naturally during organ development, cancer invasion, or tissue regeneration.

biophysics↗

bioRxiv2025

Mechanical control of histone serotonylation initiates neural crest migration in vivo

Collective cell migration (CCM) is pivotal in several biological contexts, and posttranslational modifications of histones are essential to initiate this process1-3. Here, we show that a recently discovered chromatin mark, termed histone serotonylation4, is involved in the collective migration of cranial neural crest cells - an embryonic multipotent stem cell population5. Our in vivo data reveal that histone serotonylation appears in neural crest cells just before they start migrating and that its occurrence is essential to initiate their CCM. Surprisingly, we found that stiffening of the neural crest migratory substrate, the mesoderm, induces histone serotonylation by promoting nuclear translocation of transglutaminase 2 (Tgm2), the enzyme responsible for adding serotonin to histones4. Moreover, mechanical and molecular perturbations demonstrate that mechanical shuttling of Tgm2 into the nucleus, with concomitant increases in histone serotonylation, are both required and sufficient to allow CCM in vivo. Furthermore, integrated chromatin immunoprecipitation and RNA sequencing analyses uncover a transcriptional module, which is enabled by histone serotonylation in response to mesoderm stiffening. Altogether, our results provide in vivo evidence showing that tissue stiffening leads to increased levels of histone serotonylation to reinforce permissive patterns of gene expression, supporting the switch from non-migratory to migratory cell states.

developmental biology↗

bioRxiv2025

Piezo1-Yap1 signalling translates tissue mechanics into regenerative cell states.

Epimorphic regeneration encompasses several stages, such as wound healing, formation of a regenerative bud and regenerative outgrowth. The signatures that define each stage have been well studied, yet little is known about the mechanisms that coordinate cell state transitions across regenerative stages. Here, we show that stiffening of wounded epithelial tissues is essential for the formation of a prospective regenerative bud and, in turn, for the transition from wound healing to bud formation. Mechanistically, to detect prospective bud stiffening, cells use a mechanosensitive cascade involving Piezo1-dependent Yap1 activation. We also determined that this cascade is required for the acquisition of a transcriptional profile that endows bud cells with regenerative competence. Notably, the activation of this Piezo1-Yap1 mechanosensitive cascade in nonregenerative contexts is sufficient to induce the formation of competent bud-like structures, which are sufficient to drive de novo regeneration in these otherwise incompetent tissues. Taken together, our results reveal a mechanical state at the boundary between wound healing and regenerative bud formation, which is essential for synchronizing the transition between these pivotal stages of regeneration. More broadly, these findings support the general idea that the physical properties of tissues integrate with molecular frameworks to actuate cell state transitions during morphogenesis.

developmental biology↗

bioRxiv2024

Nuclear deformability facilitates apical nuclear migration in the developing zebrafish retina

Nuclear positioning is an important aspect of cell and developmental biology. One example is the apical positioning of nuclei in retinal and other neuroepithelia. Here, apical nuclear migration is crucial for correct tissue formation. Cytoskeletal mechanisms that drive nuclei to the apical side have been explored. Yet, whether also nuclear properties influence apical nuclear migration remained comparatively less understood. Lamin A/C expression levels have been shown to be directly related to nuclear deformability. Further, it was shown that many nuclei in early development, including neuroepithelial nuclei, express only low levels of Lamin A/C. Thus, we asked whether increased expression of Lamin A in the densely packed zebrafish retinal neuroepithelium affects nuclear migration phenomena. We find that overexpressing Lamin A in retinal nuclei of single cells or in the whole tissue increased nuclear stiffness and consequently impaired apical positioning. Interestingly, also nuclei of control cells embedded in a Lamin A overexpressing environment displayed impaired apical nuclear migration. When Lamin A is overexpressed at the tissue level this further leads to a delay in mitotic entry. Thus, nuclear material properties, within cells but also in the surrounding environment, can influence nuclear and cell behavior in densely packed neuroepithelia. Overall, this work quantitatively shows a relevance of low Lamin A/C levels in early neuroepithelial development. These findings are most likely also applicable for other developing tissues which feature nuclear and cell motion through crowded environments.

developmental biology↗

bioRxiv2021

Stretch-induced endogenous electric fields drive neural crest directed collective cell migration in vivo

Directed collective cell migration (dCCM) is essential for morphogenesis1, 2. Cell clusters migrate in inherently complex in vivo environments composed of chemical, electrical, mechanical as well as topological features. While these environmental factors have been shown to allow dCCM in vitro, our understanding of dCCM in vivo is mostly limited to chemical guidance3. Thus, despite its wide biological relevance, the mechanisms that guide dCCM in vivo remain unclear. To address this, we study endogenous electric fields in relation to the migratory environment of the Xenopus laevis cephalic neural crest, an embryonic cell population that collectively and directionally migrates in vivo4, and whose migratory mode has been linked to cancer invasion and metastasis5. Combining bioelectrical, biomechanical and molecular tools, we show that endogenous electric fields drive neural crest dCCM via electrotaxis in vivo. Moreover, we identify the voltage-sensitive phosphatase 1 (Vsp1) as a key component of the molecular mechanism used by neural crest cells to transduce electric fields into a directional cue in vivo. Furthermore, Vsp1 function is specifically required for electrotaxis, being dispensable for cell motility and chemotaxis. Finally, we reveal that endogenous electric fields are mechanoelectrically established. Mechanistically, convergent extension movements of the neural fold generate membrane tension, which in turn opens stretch-activated channels to mobilise the ions required to fuel electric fields. Overall, our results reveal a mechanism of cell guidance, where electrotaxis emerges from the mechanoelectrical and molecular interplay between neighbouring tissues. More broadly, our data contribute to validate the, otherwise understudied, functions of endogenous bioelectrical stimuli in morphogenetic processes6.

developmental biology↗

bioRxiv2021

Microtubule deacetylation reduces cell stiffness to allow the onset of collective cell migration in vivo

Embryogenesis, tissue repair and cancer metastasis rely on collective cell migration (CCM). In vitro studies propose that migrating cells are stiffer when exposed to stiff substrates, known to allow CCM, but softer when plated in compliant non-permissive surfaces. Here, by combining in vivo atomic force microscopy (iAFM) and modelling we reveal that to collectively migrate in vivo, cells require to dynamically decrease their stiffness in response to the temporal stiffening of their native substrate. Moreover, molecular and mechanical perturbations of embryonic tissues uncover that this unexpected cell mechanical response is achieved by a new mechanosensitive pathway involving Piezo1-mediated microtubule deacetylation. Finally, lowering microtubule acetylation and consequently cell stiffness was sufficient to allow CCM in soft non-permissive substrates, suggesting that a fixed value of substrate stiffness is not as essential for CCM as it is reaching an optimal cell-to-substrate stiffness value. These in vivo insights on cell-to-substrate mechanical interplay have major implications to our re-interpretation of physiological and pathological contexts.

cell biology↗