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De la Fuente, I. M.

Publications and source records attributed to De la Fuente, I. M..

5 recordsLinked to original sources

Systemic and kinematic properties of Amoeba proteus migration correlate strongly across environments

Recent work has shown that cell migration is a systemic property of the whole cell, yet how the different properties of a migratory trajectory relate to one another remains largely uncharacterized. Here we quantified the migration of 150 Amoeba proteus cells under three experimental scenarios (absence of stimuli, a direct-current electric field, and a chemotactic peptide gradient) with eleven metrics that describe either the systemic dynamics of the trajectory (long-range correlations, long-term persistence, super-diffusive exploration, regularity of the move steps and memory of the velocity) or its kinematic output (net displacement, straightness and speed). Screening all 55 metric pairs for statistical dependence with distance covariance identified six couplings that held in all three experimental scenarios, besides the pairs linked by definition. Long-term persistence and super-diffusive exploration were coupled with each other, in agreement with the scaling relation expected for self-similar trajectories, and each of them was coupled with the net displacement and the straightness of the trajectory: more persistent and more super-diffusive cells moved farther and along straighter paths. In addition, the long-range correlations of the move steps were coupled with the memory of speed between consecutive steps. All six couplings were positive and monotonic, with no trend reversal over the observed range. The stimuli shifted six of the eleven metrics, the electric field mainly increasing the straightness and the net displacement of the trajectories and the chemical gradient mainly increasing the speed memory, but they left the six couplings intact and reorganized part of the dependence structure around speed. These results show that several systemic and kinematic properties of Amoeba proteus migration are not independent observables but vary together as parts of an integrated system whose couplings are preserved across environments.

cell biology↗

Quantifying the Information Capacity of DNA Methylation as an Epigenetic Memory System

The information content of the genome has been extensively analyzed. However, a comparable quantitative framework for DNA methylation is still lacking. Without such quantification, the magnitude of this regulatory and dynamic epigenetic structure remains conceptually imprecise, even though methylation dysregulation is strongly linked to disease-related phenotypes and altered cellular identity. Here we address this gap by applying Shannon information theory to DNA methylation. We first consider methylation marks as binary or probabilistic regulatory states and estimate the theoretical upper-bound information capacity of the human methylome under simplifying assumptions. We then progressively refine this estimate by incorporating biologically relevant constraints, including methylation bias, bimodal methylation distributions, local CpG correlation, genomic regulatory class, and cell-type-discriminative methylation patterns. This approach allows us to distinguish between theoretical methylation capacity, statistical methylation entropy, and biologically interpretable regulatory information. Finally, we consider methylation information from a discriminative perspective, analyzing its contribution to distinguishing cell types and regulatory cellular states. Within this framework, mutual information between methylation patterns and cell identity provides a biologically constrained estimate of methylations role as an epigenetic identity code. Our layered analysis reconciles megabit-scale methylome capacity with compact, biologically interpretable identity signatures. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/735086v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@44dc66org.highwire.dtl.DTLVardef@e1ba03org.highwire.dtl.DTLVardef@17b2acborg.highwire.dtl.DTLVardef@136b1ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

Systemic migrations in enucleated cells

Directional locomotion is a fundamental characteristic of many cells with great relevance in essential physiological and human pathological processes. For decades, research efforts have focused on studying specific individual processes and their corresponding biomolecular components involved in cellular locomotion movements. However, the notion that migratory displacements are functionally integrated and regulated at the systemic level has never been recognized. Recently, we have shown that locomotion movements correspond to an emergent systemic behavior which depends on a complex integrated self-organized system carefully regulated at a global cellular level. Here, to study the forces driving the locomotion movement of the cell, and to corroborate the thesis on the systemic character of the cellular migratory responses we have carried out an extensive study of locomotion movements with enucleated cells (cytoplasts) belonging to Amoeba proteus. The migratory behavior of both enucleated and non-enucleated cells has been individually studied in four different scenarios: in absence of stimuli, under a galvanotactic field, in chemotactic gradient, and under very complex conditions such as simultaneous galvanotactic and chemotactic stimuli. All these experimental displacement trajectories, obtained on flat two-dimensional surfaces, have been analyzed using advanced non-linear quantitative approaches. Our results show that both non-enucleated amoebas and cytoplasts display the same complex kind of dynamic structure in their migratory trajectories. The locomotion displacements of enucleated cells are regulated by complex self-organized integrative dynamics, modulated at a global-systemic level which seems to depend on the cooperative interaction of most, if not all, molecular components of cells.

systems biology↗

Forces directing the systemic correlations of cell migration

Directional motility is an essential property of cells. Despite its enormous relevance in many fundamental physiological and pathological processes, how cells control their locomotion movements remains an unresolved question. Here we have addressed the systemic processes driving the directed locomotion of cells. Specifically, we have performed an exhaustive study analyzing the trajectories of 700 individual cells belonging to three different species (Amoeba proteus, Metamoeba leningradensis and Amoeba borokensis) in four different scenarios: in absence of stimuli, under an electric field (galvanotaxis), in a chemotactic gradient (chemotaxis), and under simultaneous galvanotactic and chemotactic stimuli. All movements were analyzed using advanced quantitative tools. The results show that the trajectories are mainly characterized by coherent integrative responses that operate at the global cellular scale. These systemic migratory movements depend on the cooperative non-linear interaction of most, if not all, molecular components of cells. SignificanceCellular migration is a cornerstone issue in many human physiological and pathological processes. For years, the scientific attention has been focused on the individualized study of the diverse molecular parts involved in directional motility; however, locomotion movements have never been regarded as a systemic process that operates at a global cellular scale. In our quantitative experimental analysis essential systemic properties underlying locomotion movements were detected. Such emergent systemic properties are not found specifically in any of the molecular parts, partial mechanisms, or individual processes of the cell. Cellular displacements seem to be regulated by integrative processes operating at systemic level.

systems biology↗

Unicellular associative conditioning: an interspecies analysis

The capacity to learn new systemic behaviour is a fundamental issue to understand the adaptive mechanisms involved in cellular evolution. We have recently observed, in a preliminary analysis, the emergence of conditioned behaviour in individual amoebae cells. In these experiments, cells were able to acquire new migratory conduct and remember it for long periods of their cellular cycle, forgetting it later on. Here, following a similar conceptual framework of Pavlovs experiments, we have exhaustively studied the migration trajectories of more than 2000 individual cells belonging to three different species: Amoeba proteus, Metamoeba leningradensis, and Amoeba borokensis. Fundamentally, we have analysed several properties of conditioned cells, such as the intensity of the responses, the directionality persistence, the total distance traveled, the directionality ratio, the average speed, and the persistence times. We have observed that these three species can modify the systemic response to a specific stimulus by associative conditioning. Our main analysis shows that such new behaviour is very robust and presents a similar structure of migration patterns in the three species, which was characterized by the presence of conditioning for long periods, remarkable straightness in their trajectories and strong directional persistence. Our quantitative results, compared with other studies on complex cellular responses in bacteria, protozoa, fungus-like organisms and metazoans, allow us to conclude that cellular associative conditioning might be a widespread characteristic of unicellular organisms. This finding could be essential to understand some key evolutionary principles involved in increasing the cellular adaptive fitness to microenvironments.

systems biology↗