Jerome Mathe - Academia.edu (original) (raw)
Papers by Jerome Mathe
The current-voltage characteristics of the alpha-Hemolysin protein pore during the passage of sin... more The current-voltage characteristics of the alpha-Hemolysin protein pore during the passage of single-stranded DNA under varying ionic strength, C, are studied experimentally. We observe strong blockage of the current, weak super-linear growth of the current as a function of voltage, and a minimum of the current as a function of C. These observations are interpreted as the result of the ion electrostatic self-energy barrier originating from the large difference in the dielectric constants of water and the lipid bilayer. The dependence of DNA capture rate on C also agrees with our model.
AIP Conference Proceedings, 2009
In recent years, nanopores nave become an important tool to study the properties of single biomol... more In recent years, nanopores nave become an important tool to study the properties of single biomolecules in ionic solutions. The technique is based on the translocation of biomolecules through pores of comparable size, which are recorded as changes in the pore conductance. Among the various topics that can be studied with this technique are DNA unzipping and protein denaturation Various
Biophysical Journal, 2015
In this mini-review we introduce and discuss a new method, at single molecule level, to study the... more In this mini-review we introduce and discuss a new method, at single molecule level, to study the protein folding and protein stability, with a nanopore coupled to an electric detection. Proteins unfolded or partially folded passing through one channel submitted to an electric field, in the presence of salt solution, induce different detectable blockades of ionic current. Their duration depends on protein conformation. For different studies proteins through nanopores, completely unfolded proteins induce only short current blockades. Their frequency increases as the concentration of denaturing agent or temperature increases, following a sigmoidal denaturation curve. The geometry or the net charge of the nanopores does not alter the unfolding transition, sigmoidal unfolding curve and half denaturing concentration or half temperature denaturation. A destabilized protein induces a shift of the unfolding curve towards the lower values of the denaturant agent compared to the wild type protein.Partially folded proteins exhibit very long blockades in nanopores. The blockade duration decreases when the concentration of denaturing agent increases. The variation of these blockades could be associated to a possible glassy behaviour.
Biophysical Journal, 2014
Methods in enzymology, 2010
The time-dependent response of individual biomolecular complexes to an applied force can reveal t... more The time-dependent response of individual biomolecular complexes to an applied force can reveal their mechanical properties, interactions with other biomolecules, and self-interactions. In the past decade, a number of single-molecule methods have been developed and applied to a broad range of biological systems, such as nucleic acid complexes, enzymes and proteins in the skeletal and cardiac muscle sarcomere. Nanopore force spectroscopy (NFS) is an emerging single-molecule method, which takes advantage of the native electrical charge of biomolecule to exert a localized bond-rupture force and measure the biomolecule response. Here, we review the basic principles of the method and discuss two bond breakage modes utilizing either a fixed voltage or a steady voltage ramp. We describe a unified theoretical formalism to extract kinetic information from the NFS data, and illustrate the utility of this formalism by analyzing data from nanopore unzipping of individual DNA hairpin molecules, ...
Physical Review Letters, 2014
Methods in Molecular Biology, 2012
We present here an overview on unfolding of biomolecular structures as DNA double strands or prot... more We present here an overview on unfolding of biomolecular structures as DNA double strands or protein folds. After some theoretical considerations giving orders of magnitude about transport timescales through pores, forces involved in unzipping processes … we present our experiments on DNA unzipping or protein unfolding using a nanopore. We point out the diffi culties that can be encountered during these experiments, such as the signal analysis problems, noise issues, or experimental limitations of such system.
The Journal of Physical Chemistry C, 2011
Protein & Peptide Letters, 2014
Proceedings of the National Academy of Sciences, 2005
We characterize the voltage-driven motion and the free motion of single-stranded DNA (ssDNA) mole... more We characterize the voltage-driven motion and the free motion of single-stranded DNA (ssDNA) molecules captured inside the ≈1.5-nm α-hemolysin pore, and show that the DNA–channel interactions depend strongly on the orientation of the ssDNA molecules with respect to the pore. Remarkably, the voltage-free diffusion of the 3′-threaded DNA (in the trans to cis direction) is two times slower than the corresponding 5′-threaded DNA having the same poly(dA) sequence. Moreover, the ion currents flowing through the blocked pore with either a 3′-threaded DNA or 5′ DNA differ by ≈30%. All-atom molecular dynamics simulations of our system reveal a microscopic mechanism for the asymmetric behavior. In a confining pore, the ssDNA straightens and its bases tilt toward the 5′ end, assuming an asymmetric conformation. As a result, the bases of a 5′-threaded DNA experience larger effective friction and forced reorientation that favors co-passing of ions. Our results imply that the translocation proces...
Physical Review Letters, 2008
Physical Review Letters, 2006
The current-voltage characteristics of the alpha-Hemolysin protein pore during the passage of sin... more The current-voltage characteristics of the alpha-Hemolysin protein pore during the passage of single-stranded DNA under varying ionic strength, C, are studied experimentally. We observe strong blockage of the current, weak super-linear growth of the current as a function of voltage, and a minimum of the current as a function of C. These observations are interpreted as the result of the ion electrostatic self-energy barrier originating from the large difference in the dielectric constants of water and the lipid bilayer. The dependence of DNA capture rate on C also agrees with our model.
AIP Conference Proceedings, 2009
In recent years, nanopores nave become an important tool to study the properties of single biomol... more In recent years, nanopores nave become an important tool to study the properties of single biomolecules in ionic solutions. The technique is based on the translocation of biomolecules through pores of comparable size, which are recorded as changes in the pore conductance. Among the various topics that can be studied with this technique are DNA unzipping and protein denaturation Various
Biophysical Journal, 2015
In this mini-review we introduce and discuss a new method, at single molecule level, to study the... more In this mini-review we introduce and discuss a new method, at single molecule level, to study the protein folding and protein stability, with a nanopore coupled to an electric detection. Proteins unfolded or partially folded passing through one channel submitted to an electric field, in the presence of salt solution, induce different detectable blockades of ionic current. Their duration depends on protein conformation. For different studies proteins through nanopores, completely unfolded proteins induce only short current blockades. Their frequency increases as the concentration of denaturing agent or temperature increases, following a sigmoidal denaturation curve. The geometry or the net charge of the nanopores does not alter the unfolding transition, sigmoidal unfolding curve and half denaturing concentration or half temperature denaturation. A destabilized protein induces a shift of the unfolding curve towards the lower values of the denaturant agent compared to the wild type protein.Partially folded proteins exhibit very long blockades in nanopores. The blockade duration decreases when the concentration of denaturing agent increases. The variation of these blockades could be associated to a possible glassy behaviour.
Biophysical Journal, 2014
Methods in enzymology, 2010
The time-dependent response of individual biomolecular complexes to an applied force can reveal t... more The time-dependent response of individual biomolecular complexes to an applied force can reveal their mechanical properties, interactions with other biomolecules, and self-interactions. In the past decade, a number of single-molecule methods have been developed and applied to a broad range of biological systems, such as nucleic acid complexes, enzymes and proteins in the skeletal and cardiac muscle sarcomere. Nanopore force spectroscopy (NFS) is an emerging single-molecule method, which takes advantage of the native electrical charge of biomolecule to exert a localized bond-rupture force and measure the biomolecule response. Here, we review the basic principles of the method and discuss two bond breakage modes utilizing either a fixed voltage or a steady voltage ramp. We describe a unified theoretical formalism to extract kinetic information from the NFS data, and illustrate the utility of this formalism by analyzing data from nanopore unzipping of individual DNA hairpin molecules, ...
Physical Review Letters, 2014
Methods in Molecular Biology, 2012
We present here an overview on unfolding of biomolecular structures as DNA double strands or prot... more We present here an overview on unfolding of biomolecular structures as DNA double strands or protein folds. After some theoretical considerations giving orders of magnitude about transport timescales through pores, forces involved in unzipping processes … we present our experiments on DNA unzipping or protein unfolding using a nanopore. We point out the diffi culties that can be encountered during these experiments, such as the signal analysis problems, noise issues, or experimental limitations of such system.
The Journal of Physical Chemistry C, 2011
Protein & Peptide Letters, 2014
Proceedings of the National Academy of Sciences, 2005
We characterize the voltage-driven motion and the free motion of single-stranded DNA (ssDNA) mole... more We characterize the voltage-driven motion and the free motion of single-stranded DNA (ssDNA) molecules captured inside the ≈1.5-nm α-hemolysin pore, and show that the DNA–channel interactions depend strongly on the orientation of the ssDNA molecules with respect to the pore. Remarkably, the voltage-free diffusion of the 3′-threaded DNA (in the trans to cis direction) is two times slower than the corresponding 5′-threaded DNA having the same poly(dA) sequence. Moreover, the ion currents flowing through the blocked pore with either a 3′-threaded DNA or 5′ DNA differ by ≈30%. All-atom molecular dynamics simulations of our system reveal a microscopic mechanism for the asymmetric behavior. In a confining pore, the ssDNA straightens and its bases tilt toward the 5′ end, assuming an asymmetric conformation. As a result, the bases of a 5′-threaded DNA experience larger effective friction and forced reorientation that favors co-passing of ions. Our results imply that the translocation proces...
Physical Review Letters, 2008
Physical Review Letters, 2006