0000000000005154
AUTHOR
Michael Levin
showing 14 related works from this author
Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate
2021
Simple Summary Electric potential patterns across tissues are instructive for development, regeneration, and tumorigenesis because they can influence transcription, migration, and differentiation through biochemical and biomechanical downstream processes. Determining the origins of the spatial domains of distinct potential, which in turn decide anatomical features such as limbs, eyes, brain, and heart, is critical to a mature understanding of how bioelectric signaling drives morphogenesis. We studied theoretically how connexin proteins with different voltage-gated gap junction conductances can maintain multicellular regions at distinct membrane potentials. We analyzed a minimal model that i…
Morphology changes induced by intercellular gap junction blocking: A reaction-diffusion mechanism.
2021
Complex anatomical form is regulated in part by endogenous physiological communication between cells; however, the dynamics by which gap junctional (GJ) states across tissues regulate morphology are still poorly understood. We employed a biophysical modeling approach combining different signaling molecules (morphogens) to qualitatively describe the anteroposterior and lateral morphology changes in model multicellular systems due to intercellular GJ blockade. The model is based on two assumptions for blocking-induced patterning: (i) the local concentrations of two small antagonistic morphogens diffusing through the GJs along the axial direction, together with that of an independent, uncouple…
Bioelectrical coupling in multicellular domains regulated by gap junctions: A conceptual approach.
2018
We review the basic concepts involved in bioelectrically-coupled multicellular domains, focusing on the role of membrane potentials (Vmem). In the first model, single-cell Vmem is modulated by two generic polarizing and depolarizing ion channels, while intercellular coupling is implemented via voltage-gated gap junctions. Biochemical and bioelectrical signals are integrated via a feedback loop between Vmem and the transcription and translation of a protein forming an ion channel. The effective rate constants depend on the single-cell Vmem because these potentials modulate the local concentrations of signaling molecules and ions. This electrochemically-based idealization of the complex bioph…
Bioelectrical model of head-tail patterning based on cell ion channels and intercellular gap junctions
2020
Robust control of anterior-posterior axial patterning during regeneration is mediated by bioelectric signaling. However, a number of systems-level properties of bioelectrochemical circuits, including stochastic outcomes such as seen in permanently de-stabilized "cryptic" flatworms, are not completely understood. We present a bioelectrical model for head-tail patterning that combines single-cell characteristics such as membrane ion channels with multicellular community effects via voltage-gated gap junctions. It complements the biochemically-focused models by describing the effects of intercellular electrochemical coupling, cutting plane, and gap junction blocking of the multicellular ensemb…
ARIA���EAACI statement on asthma and COVID���19 (June 2, 2020)
2021
Artículo con numerosos autores sólo se mencionan el primero y el de la UAM
Bioelectrical Coupling of Single-Cell States in Multicellular Systems.
2020
The spatiotemporal distributions of signaling ions and molecules that modulate biochemical pathways in nonexcitable cells are influenced by multicellular electric potentials. These potentials act as distributed controllers encoding instructive spatial patterns in development and regeneration. We review experimental facts and discuss recent bioelectrical models that provide new physical insights and complement biochemical approaches. Single-cell states are modulated at the multicellular level because of the coupling between neighboring cells, thus allowing memories and multicellular patterns. The model is based on (i) two generic voltage-gated ion channels that promote the polarized and depo…
Community effects allow bioelectrical reprogramming of cell membrane potentials in multicellular aggregates: Model simulations.
2020
Bioelectrical patterns are established by spatiotemporal correlations of cell membrane potentials at the multicellular level, being crucial to development, regeneration, and tumorigenesis. We have conducted multicellular simulations on bioelectrical community effects and intercellular coupling in multicellular aggregates. The simulations aim at establishing under which conditions a local heterogeneity consisting of a small patch of cells can be stabilized against a large aggregate of surrounding identical cells which are in a different bioelectrical state. In this way, instructive bioelectrical information can be persistently encoded in spatiotemporal patterns of separated domains with diff…
Management of anaphylaxis due to COVID-19 vaccines in the elderly
2021
Submitted by (omml@ubi.pt) on 2021-07-05T10:47:24Z No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2021-07-05T10:49:11Z (GMT) No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Rejected by Pessoa (pfep@ubi.pt), reason: Rever os nomes dos autores. Depois da correção é só voltar a submeter. on 2021-07-05T10:54:19Z (GMT) Submitted by (omml@ubi.pt) on 2021-07-05T11:52:24Z No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffab…
HCN2 Channel-Induced Rescue of Brain Teratogenesis via Local and Long-Range Bioelectric Repair
2020
Embryonic exposure to the teratogen nicotine results in brain defects, by disrupting endogenous spatial pre patterns necessary for normal brain size and patterning. Extending prior work in Xenopus laevis that showed that misexpression of ion channels can rescue morphogenesis, we demonstrate and characterize a novel aspect of developmental bioelectricity: channel-dependent repair signals propagate long-range across the embryo. We show that distal HCN2 channel misexpression and distal transplants of HCN2-expressing tissue, non-cell-autonomously reverse profound defects, rescuing brain anatomy, gene expression, and learning. Moreover, such rescue can be induced by small-molecule HCN2 channel a…
From non-excitable single-cell to multicellular bioelectrical states supported by ion channels and gap junction proteins: Electrical potentials as di…
2019
Endogenous bioelectric patterns within tissues are an important driver of morphogenesis and a tractable component of a number of disease states. Developing system-level understanding of the dynamics by which non-neural bioelectric circuits regulate complex downstream cascades is a key step towards both, an evolutionary understanding of ion channel genes, and novel strategies in regenerative medicine. An important capability gap is deriving rational modulation strategies targeting individual cells' bioelectric states to achieve global (tissue- or organ-level) outcomes. Here, we develop an ion channel-based model that describes multicellular states on the basis of spatio-temporal patterns of …
Synchronization of Bioelectric Oscillations in Networks of Nonexcitable Cells: From Single-Cell to Multicellular States.
2019
Biological networks use collective oscillations for information processing tasks. In particular, oscillatory membrane potentials have been observed in nonexcitable cells and bacterial communities where specific ion channel proteins contribute to the bioelectric coordination of large populations. We aim at describing theoretically the oscillatory spatiotemporal patterns that emerge at the multicellular level from the single-cell bioelectric dynamics. To this end, we focus on two key questions: (i) What single-cell properties are relevant to multicellular behavior? (ii) What properties defined at the multicellular level can allow an external control of the bioelectric dynamics? In particular,…
ARIA‐EAACI care pathways for allergen immunotherapy in respiratory allergy
2021
Funding Information: BSreports personal fees from Allergopharma, during the conduct of the study; grants from National Health Programm, grant, personal fees from Polpharma, ASTRA, personal fees from Mylan, Adamed, patient ombudsman, national Centre for Research and Development, Polish Allergology Society. Funding Information: NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. Funding Information: CA reports grants from Allergopharma, grants from Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Rese…
TBVAC2020: Advancing Tuberculosis Vaccines from Discovery to Clinical Development
2017
International audience; TBVAC2020 is a research project supported by the Horizon 2020 program of the European Commission (EC). It aims at the discovery and development of novel tuberculosis (TB) vaccines from preclinical research projects to early clinical assessment. The project builds on previous collaborations from 1998 onwards funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in attracting new partners from outstanding laboratories from all over the world, now totaling 40 institutions. Next to the development of novel vaccines, TB biomarker development is also considered an important asset to facilitate rational vaccine selection and development. In addition, …
Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19
2021
International audience; Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress. This leads to insulin resistance …