Biomedical subjects

P De Los Rios

Publications and source records attributed to P De Los Rios.

15 recordsLinked to original sources

PubMed2006

Numerical simulation of gel electrophoresis of DNA knots in weak and strong electric fields.

Gel electrophoresis allows one to separate knotted DNA (nicked circular) of equal length according to the knot type. At low electric fields, complex knots, being more compact, drift faster than simpler knots. Recent experiments have shown that the drift velocity dependence on the knot type is inverted when changing from low to high electric fields. We present a computer simulation on a lattice of a closed, knotted, charged DNA chain drifting in an external electric field in a topologically restricted medium. Using a Monte Carlo algorithm, the dependence of the electrophoretic migration of the DNA molecules on the knot type and on the electric field intensity is investigated. The results are in qualitative and quantitative agreement with electrophoretic experiments done under conditions of low and high electric fields.

Algorithms↗

PubMed2005

Slow energy relaxation of macromolecules and nanoclusters in solution.

Many systems in the realm of nanophysics from both the living and the inorganic world display slow relaxation kinetics of energy fluctuations. In this Letter we propose a general explanation for such a phenomenon, based on the effects of interactions with the solvent. Within a simple harmonic model of the system fluctuations, we demonstrate that the inhomogeneity of coupling to the solvent of the bulk and surface atoms suffices to generate a complex spectrum of decay rates. We show for myoglobin and for a metal nanocluster that the result is a complex, nonexponential relaxation dynamics.

Kinetics↗

PubMed2005

Anti-cooperativity in diffusion-controlled reactions with pairs of anisotropic domains: a model for the antigen-antibody encounter.

The encounter between anisotropic agents in diffusion-controlled reactions is a topic of very general relevance in chemistry and biology. Here we introduce a simplified model of encounter of an isotropic molecule with a pair of partially reacting agents and apply it to the encounter reaction between an antibody and its antigen. We reduce the problem to the solution of dual series relations, which can be solved iteratively, yielding the exact solution for the encounter rate constant at any desired order of accuracy. We quantify the encounter effectiveness by means of a simple indicator and show that the two binding centers systematically behave in an anti-cooperative fashion. However, we demonstrate that a reduction of the binding active sites allows the composite molecule to recover binding effectiveness, in spite of the overall reduction of the rate constant. In addition, we provide a simple formula that enables one to calculate the anti-cooperativity as a function of the size of the binding site for any values of the separation between the two active lobes and of the antigen size. Finally, some biological implications of our results are discussed.

Animals↗

PubMed2005

Dynamics of antibodies from cryo-electron tomography.

The issue of protein dynamics and its implications in the biological function of proteins are arousing greater and greater interest in molecular biology. In cryo-electron tomography experiments one takes several snapshots of a given biological macromolecule. In principle, a large enough collection of snapshots may then be used to calculate its equilibrium configuration in terms of the experimentally accessible degrees of freedom, and hence estimate its potential energy. Consequently, one could analyze the biological functions of biomolecules by directly accessing their dynamics. In this work, we analyze the results of cryo-electron tomography experiments on monoclonal murine IgG2a antibodies. With the aid of a novel software for image processing, we measure the equilibrium distribution of the angles which describe the configuration of the molecule. This helps us shed some critical light on recent results from X-ray crystallography. We then build a model of the antibody dynamics, which enables us to use the measured angular distribution in order to derive an explicit expression of the IgG potential energy. Finally, as a preliminary application of our results, we investigate the dynamical effects in the rate of formation of the antigen-antibody encounter complex. In particular, we suggest that the dynamics of antibodies operates in the direction of decreasing anticooperativity of the two antigen binding arms.

Animals↗

PubMed2004

Preferential exchange: strengthening connections in complex networks.

Many social, technological, and biological interactions involve network relationships whose outcome intimately depends on the structure of the network and on the strengths of the connections. Yet, although much information is now available concerning the structure of many networks, the strengths are more difficult to measure. Here we show that, for one particular social network, notably the e-mail network, a suitable measure of the strength of the connections can be available. We also propose a simple mechanism, based on positive feedback and reciprocity, that can explain the observed behavior and that hints toward specific dynamics of formation and reinforcement of network connections. Network data from contexts different from social sciences indicate that power-law, and generally broad, distributions of the connection strength are ubiquitous, and the proposed mechanism has a wide range of applicability.

Journal Article↗

PubMed2004

Solvent-induced micelle formation in a hydrophobic interaction model.

We investigate the aggregation of amphiphilic molecules by adapting the two-state Muller-Lee-Graziano model for water, in which a solvent-induced hydrophobic interaction is included implicitly. We study the formation of various types of micelle as a function of the distribution of hydrophobic regions at the molecular surface. Successive substitution of nonpolar surfaces by polar ones demonstrates the influence of hydrophobicity on the upper and lower critical solution temperatures. Aggregates of lipid molecules, described by a refinement of the model in which a hydrophobic tail of variable length interacts with different numbers of water molecules, are stabilized as the length of the tail increases. We demonstrate that the essential features of micelle formation are primarily solvent-induced, and are explained within a model which focuses only on the alteration of water structure in the vicinity of the hydrophobic surface regions of amphiphiles in solution.

Colloids↗

PubMed2004

Freezing immunoglobulins to see them move.

The issue of protein dynamics and its implications in the biological function of proteins are arousing greater and greater interest in different fields of molecular biology. In cryo-electron tomography experiments one may take several snapshots of a given biological macromolecule. In principle, a large enough collection of snapshots of the molecule may then be used to calculate its equilibrium configuration in terms of the experimentally accessible degrees of freedom and, hence, to estimate its potential energy. This information would be crucial in order to analyze the biological functions of biomolecules by directly accessing the relevant dynamical indicators. In this article, we analyze the results of cryo-electron tomography experiments performed on monoclonal murine IgG2a antibodies. We measure the equilibrium distribution of the molecule in terms of the relevant angular coordinates and build a mechanical model of the antibody dynamics. This approach enables us to derive an explicit expression of the IgG potential energy. Furthermore, we discuss the configuration space at equilibrium in relation to results from other techniques, and we set our discussion in the context of the current debate regarding conformation and flexibility of antibodies.

Cryoelectron Microscopy↗

PubMed2004

Oscillation modes of microtubules.

Microtubules are long, filamentous protein complexes which play a central role in several cellular physiological processes, such as cell division transport and locomotion. Their mechanical properties are extremely important since they determine the biological function. In a recently published experiment [Phys. Rev. Lett. 89 (2002) 248101], microtubule's Young's and shear moduli were simultaneously measured, proving that they are highly anisotropic. Together with the known structure, this finding opens the way to better understand and predict their mechanical behavior under a particular set of conditions. In the present study, we modeled microtubules by using the finite elements method and analyzed their oscillation modes. The analysis revealed that oscillation modes involving a change in the diameter of the microtubules strongly depend on the shear modulus. In these modes, the correlation times of the movements are just slightly shorter than diffusion times of free molecules surrounding the microtubule. It could be therefore speculated that the matching of the two timescales could play a role in facilitating the interactions between microtubules and MT associated proteins, and between microtubules and tubulins themselves.

Animals↗

PubMed2003

Effective interactions cannot replace solvent effects in a lattice model of proteins.

Protein folding and protein design are among the most challenging problems of the past ten years in biophysics and molecular biology. For a given protein, it is possible to extract, from existing protein databases, a set of specific (i.e., belonging to the investigated protein) effective amino-acid (AA) interactions able to stabilize the native state. On the other hand, attempts to find global effective AA interactions, which would be able to stabilize all proteins at once, failed. Using a simple lattice model where the solvent degrees of freedom are (semi)explicitly taken into account, we show that the absence of global effective AA interactions is due to the solvent and that on this lattice model the solvent effects cannot be reproduced by amino-acid effective interactions.

Hydrophobic and Hydrophilic Interactions↗

PubMed2002

Design of lattice proteins with explicit solvent.

Protein design is important to develop new drugs. As such, a knowledge of the correct model to use to design novel proteins is of the utmost importance. Here we show that a simple model where the solvent degrees of freedom are (semi)explicitly taken into account performs better than other existing models when compared to real data. Some consequences on the criteria to be used for protein design are discussed.

Journal Article↗

PubMed2002

Scale-free networks from varying vertex intrinsic fitness.

A new mechanism leading to scale-free networks is proposed in this Letter. It is shown that, in many cases of interest, the connectivity power-law behavior is neither related to dynamical properties nor to preferential attachment. Assigning a quenched fitness value x(i) to every vertex, and drawing links among vertices with a probability depending on the fitnesses of the two involved sites, gives rise to what we call a good-get-richer mechanism, in which sites with larger fitness are more likely to become hubs (i.e., to be highly connected).

Algorithms↗

PubMed2001

Cold and warm swelling of hydrophobic polymers.

We introduce a polymer model where the transition from swollen to compact configurations is due to interactions between the monomers and the solvent. These interactions are the origin of the effective attractive interactions between hydrophobic amino acids in proteins. We find that in the low and high temperature phases polymers are swollen, and there is an intermediate phase where the most favorable configurations are compact. We argue that such a model captures in a single framework both the cold and the warm denaturation experimentally detected for thermosensitive polymers and for proteins.

Journal Article↗

PubMed2000

Expression and release of insulin-like growth factor binding proteins in isolated epiphyseal growth plate chondrocytes from the ovine fetus.

Insulin-like growth factor-II (IGF-II) is an autocrine modulator of epiphyseal chondrogenesis in the fetus. The cellular availability of IGFs are influenced by the IGF-binding proteins (IGFBPs). In this study, we investigated the control of expression and release of IGFBPs from isolated epiphyseal growth plate chondrocytes from the ovine fetus by hormones and growth factors implicated in the chondrogenic process. Chondrocytes were isolated from the proliferative zone of the fetal ovine proximal tibial growth plate and maintained in monolayer culture at early passage number. Culture media conditioned by chondrocytes under basal conditions released IGFBPs of 24, 34, and 29 kDa, and a less abundant species of 39-43 kDa that were identified immunologically as IGFBP-4, IGFBP-2, IGFBP-5, and IGFBP-3, respectively. Messenger RNAs encoding each species were identified by Northern blot analysis within chondrocytes, as was mRNA encoding IGFBP-6. Exposure to IGF-I or IGF-II (13 or 26 nM) caused an increase in expression and release of IGFBP-3. The release of IGFBP-2 and IGFBP-5 were also potentiated without changes to steady state mRNA, and for IGFBP-5 this was due in part to a release from the cell membrane in the presence of IGF-II. Insulin (16.7 or 167 nM) selectively increased mRNA and the release of IGFBP-3, while cortisol (1 or 5 microM) inhibited both mRNA and release of IGFBP-2 and IGFBP-5. Transforming growth factor-beta1 (TGF-beta1) (0.1 or 0.2 nM) increased the expression and release of IGFBP-3, and caused an increase in mRNAs encoding IGFBP-2 and IGFBP-5. Neither growth hormone (GH), fibroblast growth factor-2, nor thyroxine (T(4)) had any effect on IGFBP expression or release. The results suggest that IGFBP expression and release within the developing growth plate can be modulated by IGF-II and other trophic factors, thus controlling IGF availability and action.

Animals↗

PubMed2000

Statistical analysis of genealogical trees for polygamic species.

Repetitions within a given genealogical tree provide some information about the degree of consanguinity of a population. They can be analyzed with techniques usually employed in statistical physics when dealing with fixed point transformations. In particular, we show that the tree features strongly depend on the fractions of males and females in the population, and also on the offspring probability distribution. We check different possibilities, some of them relevant to human groups, and compare them with simulations.

Animals↗

PubMed1999

Levy-nearest-neighbors Bak-Sneppen model.

We study a random neighbor version of the Bak-Sneppen model, where "nearest neighbors" are chosen according to a probability distribution decaying as a power law of the distance from the active site, P(x) approximately x-x(ac)(-omega). All of the exponents characterizing the self-organized critical state of this model depend on the exponent omega. As omega-->1 we recover the usual random nearest-neighbor version of the model. The pattern of results obtained for a range of values of omega is also compatible with the results of simulations of the original BS model in high dimensions. Moreover, our results suggest a critical dimension dc=6 for the Bak-Sneppen model, in contrast with previous claims.

Journal Article↗