Research

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22 pages, 8519 KiB

Open AccessArticle

Neuronal Cultures: Exploring Biophysics, Complex Systems, and Medicine in a Dish

by Jordi Soriano

Biophysica 2023, 3(1), 181-202; https://doi.org/10.3390/biophysica3010012 - 10 Mar 2023

Cited by 4 | Viewed by 2375

Neuronal cultures are one of the most important experimental models in modern interdisciplinary neuroscience, allowing to investigate in a control environment the emergence of complex behavior from an ensemble of interconnected neurons. Here, I review the research that we have conducted at the [...] Read more.

Neuronal cultures are one of the most important experimental models in modern interdisciplinary neuroscience, allowing to investigate in a control environment the emergence of complex behavior from an ensemble of interconnected neurons. Here, I review the research that we have conducted at the neurophysics laboratory at the University of Barcelona over the last 15 years, describing first the neuronal cultures that we prepare and the associated tools to acquire and analyze data, to next delve into the different research projects in which we actively participated to progress in the understanding of open questions, extend neuroscience research on new paradigms, and advance the treatment of neurological disorders. I finish the review by discussing the drawbacks and limitations of neuronal cultures, particularly in the context of brain-like models and biomedicine. Full article

(This article belongs to the Special Issue State-of-the-Art Biophysics in Spain)

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19 pages, 23226 KiB

Open AccessArticle

Genotype-to-Protein Map and Collective Adaptation in a Viral Population

by Ariadna Villanueva, Henry Secaira-Morocho, Luis F. Seoane, Ester Lázaro and Susanna Manrubia

Biophysica 2022, 2(4), 381-399; https://doi.org/10.3390/biophysica2040034 - 27 Oct 2022

Cited by 1 | Viewed by 1799

Abstract

Viral populations are large and highly heterogeneous. Despite the evolutionary relevance of such heterogeneity, statistical approaches to quantifying the extent to which viruses maintain a high genotypic and/or phenotypic diversity have been rarely pursued. Here, we address this issue by analyzing a nucleotide-to-protein [...] Read more.

Viral populations are large and highly heterogeneous. Despite the evolutionary relevance of such heterogeneity, statistical approaches to quantifying the extent to which viruses maintain a high genotypic and/or phenotypic diversity have been rarely pursued. Here, we address this issue by analyzing a nucleotide-to-protein sequence map through deep sequencing of populations of the Q

β

phage adapted to high temperatures. Tens of thousands of different sequences corresponding to two fragments of the gene coding for the viral replicase were recovered. A diversity analysis of two independent populations consistently revealed that about

40 %

of the mutations identified caused changes in protein amino acids, leading to an almost complete exploration of the protein neighborhood of (non-silent) mutants at a distance of one. The functional form of the empirical distribution of phenotype abundance agreed with analytical calculations that assumed random mutations in the nucleotide sequence. Our results concur with the idea that viral populations maintain a high diversity as an efficient adaptive mechanism and support the hypothesis of universality for a lognormal distribution of phenotype abundances in biologically meaningful genotype–phenotype maps, highlighting the relevance of entropic effects in molecular evolution. Full article

(This article belongs to the Special Issue State-of-the-Art Biophysics in Spain)

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Review

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14 pages, 2020 KiB

Open AccessReview

Biological Calorimetry: Old Friend, New Insights

by Olga Abian, Sonia Vega and Adrian Velazquez-Campoy

Biophysica 2023, 3(1), 21-34; https://doi.org/10.3390/biophysica3010002 - 20 Jan 2023

Cited by 2 | Viewed by 1836

Abstract

Calorimetry is an old experimental technique (first instrument developed in S. XVIII), but it is broadly used and still provides key information for understanding biological processes at the molecular level, particularly, cooperative phenomena in protein interactions. Here, we review and highlight some key [...] Read more.

Calorimetry is an old experimental technique (first instrument developed in S. XVIII), but it is broadly used and still provides key information for understanding biological processes at the molecular level, particularly, cooperative phenomena in protein interactions. Here, we review and highlight some key aspects of biological calorimetry. Several biological systems will be described in which calorimetry was instrumental for modeling the behavior of the protein and obtaining further biological insight. Full article

(This article belongs to the Special Issue State-of-the-Art Biophysics in Spain)

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20 pages, 3772 KiB

Open AccessReview

A Review of Fifteen Years Developing Computational Tools to Study Protein Aggregation

by Carlos Pintado-Grima, Oriol Bárcenas, Andrea Bartolomé-Nafría, Marc Fornt-Suñé, Valentín Iglesias, Javier Garcia-Pardo and Salvador Ventura

Biophysica 2023, 3(1), 1-20; https://doi.org/10.3390/biophysica3010001 - 18 Jan 2023

Cited by 2 | Viewed by 3017

Abstract

The presence of insoluble protein deposits in tissues and organs is a hallmark of many human pathologies. In addition, the formation of protein aggregates is considered one of the main bottlenecks to producing protein-based therapeutics. Thus, there is a high interest in rationalizing [...] Read more.

The presence of insoluble protein deposits in tissues and organs is a hallmark of many human pathologies. In addition, the formation of protein aggregates is considered one of the main bottlenecks to producing protein-based therapeutics. Thus, there is a high interest in rationalizing and predicting protein aggregation. For almost two decades, our laboratory has been working to provide solutions for these needs. We have traditionally combined the core tenets of both bioinformatics and wet lab biophysics to develop algorithms and databases to study protein aggregation and its functional implications. Here, we review the computational toolbox developed by our lab, including programs for identifying sequential or structural aggregation-prone regions at the individual protein and proteome levels, engineering protein solubility, finding and evaluating prion-like domains, studying disorder-to-order protein transitions, or categorizing non-conventional amyloid regions of polar nature, among others. In perspective, the succession of the tools we describe illustrates how our understanding of the protein aggregation phenomenon has evolved over the last fifteen years. Full article

(This article belongs to the Special Issue State-of-the-Art Biophysics in Spain)

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17 pages, 2815 KiB

Open AccessReview

Optical Tweezers to Force Information out of Biological and Synthetic Systems One Molecule at a Time

by Rebeca Bocanegra, María Ortiz-Rodríguez, Ismael Plaza Garcia-Abadillo, Carlos R-Pulido and Borja Ibarra

Biophysica 2022, 2(4), 564-580; https://doi.org/10.3390/biophysica2040047 - 09 Dec 2022

Viewed by 2173

Abstract

Over the last few decades, in vitro single-molecule manipulation techniques have enabled the use of force and displacement as controlled variables in biochemistry. Measuring the effect of mechanical force on the real-time kinetics of a biological process gives us access to the rates, [...] Read more.

Over the last few decades, in vitro single-molecule manipulation techniques have enabled the use of force and displacement as controlled variables in biochemistry. Measuring the effect of mechanical force on the real-time kinetics of a biological process gives us access to the rates, equilibrium constants and free-energy landscapes of the mechanical steps of the reaction; this information is not accessible by ensemble assays. Optical tweezers are the current method of choice in single-molecule manipulation due to their versatility, high force and spatial and temporal resolutions. The aim of this review is to describe the contributions of our lab in the single-molecule manipulation field. We present here several optical tweezers assays refined in our laboratory to probe the dynamics and mechano-chemical properties of biological molecular motors and synthetic molecular devices at the single-molecule level. Full article

(This article belongs to the Special Issue State-of-the-Art Biophysics in Spain)

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16 pages, 1743 KiB

Open AccessReview

The Forces behind Directed Cell Migration

by Isabela C. Fortunato and Raimon Sunyer

Biophysica 2022, 2(4), 548-563; https://doi.org/10.3390/biophysica2040046 - 01 Dec 2022

Cited by 3 | Viewed by 4053

Abstract

Directed cell migration is an essential building block of life, present when an embryo develops, a dendritic cell migrates toward a lymphatic vessel, or a fibrotic organ fails to restore its normal parenchyma. Directed cell migration is often guided by spatial gradients in [...] Read more.

Directed cell migration is an essential building block of life, present when an embryo develops, a dendritic cell migrates toward a lymphatic vessel, or a fibrotic organ fails to restore its normal parenchyma. Directed cell migration is often guided by spatial gradients in a physicochemical property of the cell microenvironment, such as a gradient in chemical factors dissolved in the medium or a gradient in the mechanical properties of the substrate. Single cells and tissues sense these gradients, establish a back-to-front polarity, and coordinate the migration machinery accordingly. Central to these steps we find physical forces. In some cases, these forces are integrated into the gradient sensing mechanism. Other times, they transmit information through cells and tissues to coordinate a collective response. At any time, they participate in the cellular migratory system. In this review, we explore the role of physical forces in gradient sensing, polarization, and coordinating movement from single cells to multicellular collectives. We use the framework proposed by the molecular clutch model and explore to what extent asymmetries in the different elements of the clutch can lead to directional migration. Full article

(This article belongs to the Special Issue State-of-the-Art Biophysics in Spain)

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19 pages, 2374 KiB

Open AccessReview

Characterisation of Amyloid Aggregation and Inhibition by Diffusion-Based Single-Molecule Fluorescence Techniques

by David Polanco, Alejandra Carrancho, Pablo Gracia and Nunilo Cremades

Biophysica 2022, 2(4), 506-524; https://doi.org/10.3390/biophysica2040043 - 21 Nov 2022

Viewed by 3592

Abstract

Protein amyloid aggregation has been associated with more than 50 human disorders, including the most common neurodegenerative disorders Alzheimer’s and Parkinson’s disease. Interfering with this process is considered as a promising therapeutic strategy for these diseases. Our understanding of the process of amyloid [...] Read more.

Protein amyloid aggregation has been associated with more than 50 human disorders, including the most common neurodegenerative disorders Alzheimer’s and Parkinson’s disease. Interfering with this process is considered as a promising therapeutic strategy for these diseases. Our understanding of the process of amyloid aggregation and its role in disease has typically been limited by the use of ensemble-based biochemical and biophysical techniques, owing to the intrinsic heterogeneity and complexity of the process. Single-molecule techniques, and particularly diffusion-based single-molecule fluorescence approaches, have been instrumental to obtain meaningful information on the dynamic nature of the fibril-forming process, as well as the characterisation of the heterogeneity of the amyloid aggregates and the understanding of the molecular basis of inhibition of a number of molecules with therapeutic interest. In this article, we reviewed some recent contributions on the characterisation of the amyloid aggregation process, the identification of distinct structural groups of aggregates in homotypic or heterotypic aggregation, as well as on the study of the interaction of amyloid aggregates with other molecules, allowing the estimation of the binding sites, affinities, and avidities as examples of the type of relevant information we can obtain about these processes using these techniques. Full article

(This article belongs to the Special Issue State-of-the-Art Biophysics in Spain)

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8 pages, 907 KiB

Open AccessReview

Birth and Early Steps of the Organization of Biophysics in Spain

by Félix M. Goñi

Biophysica 2022, 2(4), 498-505; https://doi.org/10.3390/biophysica2040042 - 19 Nov 2022

Viewed by 1001

Abstract

In the 1960s, Biophysics was an unheard of scientific field in Spain, and even outside Spain, the distinction between Biophysics and Molecular Biology was not clear at the time. This paper describes briefly the developments that led to the foundation of the Spanish [...] Read more.

In the 1960s, Biophysics was an unheard of scientific field in Spain, and even outside Spain, the distinction between Biophysics and Molecular Biology was not clear at the time. This paper describes briefly the developments that led to the foundation of the Spanish National Committee for Biophysics (1981) and of the Spanish Biophysical Society (1987), the incorporation of Spain into IUPAB and EBSA, and the normalized presence of Biophysics as a compulsory subject in undergraduate curricula in Spain. Full article

(This article belongs to the Special Issue State-of-the-Art Biophysics in Spain)

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