Professor, Toulouse University
manoel.manghi(at)irsamc.ups-tlse.fr
+33 5 61 55 61 77
326
My research focuses on issues at the frontier between soft matter physics and physics of living matter. The techniques used are varied and range from analytical approaches using statistical field theory, Gaussian variational approaches, transfer matrices, scaling laws, stochastic dynamics, hydrodynamic equations to Brownian dynamics or Monte Carlo numerical simulations. [numbers corresponding to publication]
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2010 Habilitation à Diriger des Recherches, Statistical physics of biological objects and electrolytes at interfaces, LPT, Univ. P. Sabatier, Toulouse.
since 02/2005 Associate Professor, LPT, Université Toulouse III -Paul Sabatier
09/2004-01/2005 Postdoctoral contract CNRS Laboratoire de Physique Théorique et Astroparticules, Montpellier
2002-2004 Postdoctoral contract in the group of Prof. R.R. Netz, Ludwig Maximilian University, Munich. Research grant from the German Alexander von Humboldt Foundation
1999-2002 Ph.D. thesis in theoretical physics, Theoretical contributions to the study of polymers at interfaces, Laboratoire Structures et Propriétés des Architectures Macromoléculaires, Université J. Fourier, Grenoble.
1995-1999 Student of the École Normale Supérieure de Lyon, France
1998 Agrégé de sciences physiques, physics option.
The aim of this Master’s program is to train high-level students in biophysics, physical chemistry, soft matter, imaging physics and the physics of societal behavior, so that they are able to tackle biological problems using the tools of physics. These tools are now widely used in the life sciences, both to observe and study living organisms (microscopy, data analysis, trajectory tracking, etc.) and to model and understand the physical mechanisms behind biological phenomena. The PFA-PMV Master’s program covers the different scales of life, from the molecular scale (DNA, membranes, etc.) to the population scale (ants, fish, humans, etc.), via the cellular scale (bacteria, etc.) and biological tissues (epithelium, blood, etc.).
Master 1 is followed by a Master 2 in Physics and Mechanics for Living Systems.
More informations at this web page
The rigidity of double-stranded DNA plays a major role in the structuring of the chromosome and thus the expression of genes, as well as in nanotechnology where DNA is used as a building block. But, how is this rigidity influenced by the presence of different types of ions? In this work, teams from the IPBS and the LPT in Toulouse responded both experimentally and theoretically to this question.
Thanks to the massive parallelization of the single-molecule technique of Tethered Particle Motion (TPM), they measured the dependence of persistence length, reflecting the stiffness of the polymer DNA, over a wide range of ions and salt concentrations. They demonstrated a unique decay for monovalent or divalent metal ions perfectly described by recent theories, which take into account the non-linear electrostatic effects as well as the finite diameter of the DNA. This study will thus make it possible to predict conformational changes of complex structures formed by DNA both in vitro and in vivo.
Reference: S. Guilbaud, L. Salomé, N. Destainville, M. Manghi, and C. Tardin, Dependence of DNA Persistence Length on Ionic Strength and Ion Type. Physical Review Letters, 122, 028102 (2019).
A.K. Dasanna, N. Destainville, J. Palmeri and M. Manghi from the LPT have studied theoretically the mechanism of DNA denaturation bubbles closure and shown that chain bending and strand diffusion are at the origin of the long closure times measured experimentally.
In the course of DNA transcription, denaturation bubbles (DNA segments where base-pairs are broken) are nucleated in DNA and an important issue concerns the closure time of such DNA « bubbles ». Experiments have measured suprisingly long closure times in the range of 20 to 100 microseconds for small bubbles of length around 20 base-pairs.
Using Brownian dynamics simulations and analytical arguments, it is shown that the closure of a pre-equilibrated bubble (a) occurs in two steps. The first step consists in a fast zipping of the initial bubble until a metastable bubble state of length around 10 base-pairs is reached (b). The driving force for this fast kinetics is the energetic gain in base-pair closure, which becomes forbidden at some point by the large bending stored in the bubble. The closure of this metastable state is then controlled by the rotational diffusion of the two stiff arms (c). For real DNAs, the closure time is found to scale as N^2.4 for DNA lengths N between 20 and 100.
Reference: A.K. Dasanna, N. Destainville, J. Palmeri and M. Manghi, Strand diffusion-limited closure of denaturation bubbles in DNA, Europhysics Letters 98, 38002 (2012)
Atomic Force Microscopy (AFM) is widely used to observe double-stranded DNA adsorbed on surfaces. In recent experiments by Wiggins et al., « anomalies » have been detected in the distribution of bending angles along DNA (which measures its flexibility) : an over-abundance of large angles were found which are not predicted by the traditional statistical model of DNA chains, the Worm-Like Chain model (see figure). N. Destainville, M. Manghi and J. Palmeri explained these anomalies by the presence of small denaturation bubbles (or kinks) facilitated by the presence of the substrate which modifies interactions between DNA base-pairs. They predict that these anomalies exist in 3D but are too weak to be detected and reconcile the apparent discrepency between observed 2D and 3D elastic properties. Hence, conclusions about 3D properties of DNA (and its companion proteins and enzymes) do not directly follow from 2D experiments by AFM.
Reference: Microscopic mechanism for experimentally observed anomalous elasticity of DNA in 2D by N. Destainville, M. Manghi and J. Palmeri, Biophysical Journal 96, 4464 (2009) arxiv0903.1826
The denaturation of the DNA polymer is a physical process in the course of which the double strand, or helix, can open locally thanks to thermal fluctuations. An opening of successive base pairs creates a denaturation bubble. Within a bubble the two fluctuating single strands have a bending rigidity 50 times weaker than that of the unopened helix. It follows that at a given temperature, DNA can explore a much larger number of geometrical configurations when in the bubble state and therefore increase its conformational entropy. In this way, it can also have a higher local curvature, for example when wrapped around a histone. The external DNA geometry will in turn influence the bubble creation process. This mutual influence naturally leads to a theoretical model coupling the local internal DNA states (open or closed base pairs) and the local curvature of the DNA chain.
Reference: Thermal Denaturation of Fluctuating DNA Driven by Bending Entropy published in J. Palmeri, M. Manghi, and N. Destainville, Physical Review Letters 99, 088103 (2007).
By coupling the elastic properties of a rotative semi-flexible nanorod and hydrodynamic interactions, which are the source of propulsion in Stokes flows, we have shown theoretically that bacterial propulsion can be reproduced in a biomimetic way. Moreover, this work sheds light on the major role played by elasticity in flagellar motion of bacteria as E. coli.
Bacterial flagella of are helical stiff polymers set in motion at their base by a rotary motor. Using Brownian dynamics simulations with full hydrodynamic interactions which take into account momentum diffusion in Stokes flow, we show that a simple straight elastic nanorod which rotates around a point undergoes at a critical torque a strongly discontinuous shape bifurcation to a helical state. It thus gives rise to a substantial forward thrust regardless of its sense of rotation. Hence, in a biomimetic context, it makes usage of helical polymer unnecessary, allowing a selection from the much wider class of straight stiff polymers. Moreover, these elastic effects could explain some observations made on E. coli, such as the polymorphic transformations of their flagella.
Reference: M. Manghi, X. Schlagberger, R.R. Netz, Propulsion with a Rotating Elastic Nanorod, Physical Review Letters, 96068101 (2006)