Research

Since the creation of the Universitat Jaume I, the research group on molecular biophysics and membrane transport phenomena has played a very active role both in the development of new lines of research and in the incorporation of new researchers, first within the Department of Experimental Sciences (until 2006) and, since 2007, in the Department of Physics.

After a first stage of research on synthetic membranes, the group has gradually shifted its interest towards biological membranes (mainly phospholipid bilayer model membranes) and, especially, towards membrane proteins that act as ionic channels. The postdoctoral stays of several members of the group at prestigious experimental (Lab. Physical and Structural Biology, NIH, Bethesda, MD, Univ. Maryland, MD, USA) and theoretical biophysics laboratories (Rush University, Chicago, IL, USA, Univ. Verona, Italy; Johns Hopkins University, Baltimore, MD, USA) have facilitated this transition.

Since then, more intensive interdisciplinary collaborations have been developed with various groups of biologists, chemists, biochemists and virologists in order to provide the necessary balance between experimental techniques and the theoretical approach.

As a result of this interaction, the group has positioned itself as a reference in ionic transport through mesoscopic ion channels, such as bacterial pores, which are the main route of beta-lactam antibiotics and, particularly in recent years, in the electrophysiology of viral proteins with channel activity, commonly known as viroporins, which are of special interest as therapeutic targets.

Research Lines

Ion transport beyond classical electrostatics: interfacial effects, lipid remodeling, nanoscale confinement and macromolecular crowding

We are interested in the fundamentals of ion transport at the nanoscale where classical electrostatic models are not enough to explain all observed phenomena.

Our research addresses interfacial effects, such as the role of access resistance that dominates in diluted electrolyte solutions. We also investigate the contribution of lipid charge, which can unexpectedly modulate the function of large channels where lipids were previously thought to be just a passive scaffold.

Furthermore, we describe how nanoscale confinement manifests in concentrated electrolyte solutions, leading to unexpected outcomes in diverse quantities like conductance, excess noise or activation energy. Finally, we explore how macromolecular crowding challenges the predictions classical predictions, necessitating new theoretical descriptions.

Selected Publications

A. Alcaraz, M.L. López, M. Queralt-Martín, V.M. Aguilella. 2017. Ion transport in confined geometries below the nanoscale. Access resistance dominates protein channel conductance in diluted solutions. ACS Nano 11: 10392-10400.

M. Queralt-Martín, M.L. López, M. Aguilella-Arzo, V.M. Aguilella, A. Alcaraz. 2018. Scaling behavior of ionic transport in membrane nanochannels. Nano Letters, 18: 6604−6610.

M. Queralt-Martín. J.J. Pérez-Grau, L.M. Alvero-González, D.A. Perini, J. Cervera, V.M. Aguilella, A. Alcaraz. 2023. Biphasic concentration patterns in ionic transport under nanoconfinement revealed in steady state and time-dependent properties. J. Chem. Phys., 158: 64701.

M. Aguilella-Arzo, D. Hoogerheide, M. Doucet, H. Wang, V.M. Aguilella. 2024. Charged biological membranes repel large neutral molecules by surface dielectrophoresis and counterion pressure. J. Am. Chem. Soc. 146: 2701−2710.

L.M. Alvero-González, M. Aguilella-Arzo, D.A. Perini, L.A. Bergdoll, M. Queralt-Martín, A. Alcaraz. 2024. Supralinear scaling behavior of ionic transport in membrane nanochannels regulated by outer surface charges. Nanoscale Adv. 6: 6344.

M. Queralt-Martín, L.M. Alvero-González, M. Aguilella-Arzo, D.A. Perini, L.A. Bergdoll, A. Alcaraz. 2026. Interfacial effects break the canonical permeability-selectivity trade-off in biological nanopores. J. Coll. Int. Sci., 703, 139266.

Biophysical characterization of channel activity: membrane proteins, peptides and other membrane-permeabilizing agents

We collaborate with laboratories worldwide to contribute to the understanding of diverse systems that share a common trait: the act by permeabilizing lipid membranes.

Our expertise stems from cutting-edge planar bilayer electrophysiology, which allows us to evaluate how each system performs—whether by forming small, highly selective ion channels, creating proteolipid structures that regulate ion transport, or inducing dynamic, controlled permeabilization events.

Our high-resolution, time-resolved technique is pivotal for understanding the molecular function of each system at the single-molecule level. We have successfully contributed to characterizing systems such as viroporins, neurotoxic peptides, bacterial effectors, and nanoparticles.

Selected Publications

J. Rojas-Palomino, J. Altuna-Alvarez, A. González-Magaña, M. Queralt-Martín, D. Albesa-Jové, A. Alcaraz. 2025. Electrophysiological dissection of the ion channel activity of the Pseudomonas aeruginosa ionophore protein toxin Tse5. Chem. Phys. Lip., 267, 105472.

A. González-Magaña, I. Tascón, J. Altuna-Alvarez, M. Queralt-Martín, J. Colautti, C. Velázquez, M. Zabala, J. Rojas-Palomino, M. Cárdenas, A. Alcaraz, J.C. Whitney, I. Ubarretxena-Belandia, D. Albesa-Jové. 2023. Structural and functional insights into the delivery of a bacterial Rhs pore-forming toxin to the membrane. Nature Communications, 14(1).

W. Surya, E. Tavares-Neto, A. Sanchis, M. Queralt-Martín, A. Alcaraz, J. Torres, V.M. Aguilella. 2023. The Complex Proteolipidic Behavior of the SARS-CoV-2 Envelope Protein Channel: Weak Selectivity and Heterogeneous Oligomerization. Int. J. Mol. Sci., 24(15).

L.M. Alvero-González, D.A. Perini, M. Queralt-Martín, A. Perálvarez-Marín, C. Viñas, A. Alcaraz. 2023. Probing electrophysiological activity of amphiphilic Dynorphin A in planar neutral membranes reveals both ion channel-like activity and neuropeptide translocation. Bioelectrochemistry, 145, 108527.

D.A. Perini, E. Parra-Ortiz, I. Varó, M. Queralt-Martín, M. Malmsten, A. Alcaraz. 2022. Surface-Functionalized Polystyrene Nanoparticles Alter the Transmembrane Potential via Ion-Selective Pores Maintaining Global Bilayer Integrity. Langmuir, 38(48), 14837–14849.

Voltage-induced closure of β-barrel channels

β-barrel channels are relatively large pores (~0.5-2 nm in diameter) that facilitate the passive transport of hydrated ions and small metabolites across membranes.

Found in the outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria, they also function as pore-forming toxins. Under high transmembrane voltages, most β-barrel channels exhibit «gating»—transitions from open to low-conducting states. Unlike flexible alpha-helical channels, β-barrel pores are rigid structures lacking a clear gating mechanism.

To date, despite years of effort, no defined closed-state structure has been identified. Our lab aims to elucidate this mechanism through deep characterization of β-barrel gating using advanced electrophysiological recordings.

Selected Publications

D.A. Perini, A. Alcaraz, M. Queralt-Martín. 2019. Lipid headgroup charge and acyl chain composition modulate closure of bacterial β-barrel channels. Int. J. Mol. Sci., 20: 674-685.

L.M. Alvero-González, D.A. Perini, M.L. López, A. Alcaraz, M. Queralt-Martín. 2026. Voltage-induced closure of β-barrel channels as electrochemical gating. Bioelectrochemistry.

Funding

ELECTROFISIOLOGÍA Y SIMULACIÓN MOLECULAR DE PROTEÍNAS VIRALES Y NEUROTÓXICAS
INSTITUTION TITLE CODE TITLE START END
CIAICO/2023/106 ELECTROFISIOLOGÍA Y SIMULACIÓN MOLECULAR DE PROTEÍNAS VIRALES Y NEUROTÓXICAS 01/09/2024 31/08/2027
TRANSPORTE MOLECULAR EN PROTEÍNAS CANAL MÁS ALLÁ DE LA ELECTROSTÁTICA: EFECTOS INTERFACIALES, REMODELACIÓN DE LÍPIDOS, CONFINAMIENTO A NANOESCALA Y CROWDING MACROMOLECULAR
INSTITUTION TITLE CODE TITLE START END
PID2022-142795NB-I00 TRANSPORTE MOLECULAR EN PROTEÍNAS CANAL MÁS ALLÁ DE LA ELECTROSTÁTICA: EFECTOS INTERFACIALES, REMODELACIÓN DE LÍPIDOS, CONFINAMIENTO A NANOESCALA Y CROWDING MACROMOLECULAR 01/09/2023 31/08/2026
ION TRANSPORT IN BIOLOGICAL ION CHANNELS: INTERFACIAL EFFECTS, NANOSCALE CONFINEMENT AND MACROMOLECULAR CROWDING
INSTITUTION TITLE CODE TITLE START END
UJI-B2022-42 ION TRANSPORT IN BIOLOGICAL ION CHANNELS: INTERFACIAL EFFECTS, NANOSCALE CONFINEMENT AND MACROMOLECULAR CROWDING 01/01/2023 31/12/2025

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