Institut de Biologie StructuraleGrenoble / France

Contact person(s) related to this article / PELLEQUER Jean-Luc

Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death


Many chronic disorders result from disrupting immune responses. An international study (6 countries) conducted by Oliver Soehnlein of LMU Munich, including the AFM team at CEA/IRIG/IBS in Grenoble, has shown that neutrophils exacerbate atherosclerosis by causing the death of smooth muscle cells under the effect of the H4 histone and that a suitable peptide is able to inhibit the process.
The initial membrane bilayers production and AFM imaging was performed by Jean-Marie Teulon and pursued by Nihel Berrebeh during her master2 internship. Nihel also imaged by AFM the inhibition of histone H4 by peptides on these bilayers.

Silvestre-Roig C, et al. (2019) Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death. Nature 569 : 236-240.


Time sequence imaging of ExlACter by AFM on supported membrane bilayers in a buffered environment. It can be seen that upon introduction of ExlACter, the roughness of the membrane increases, the average surface area of holes decreases, and the depth of holes increases from 1.5 nm in (b) to 3.4 nm in (e).
Membrane bilayers were produced and imaged with AFM by Jean-Marie Teulon using liposomes produced by Bertrand Quentin.

Bertrand Q, et al. (2020) Exolysin (ExlA) from Pseudomonas aeruginosa punctures holes into target membranes using a “molten globule” domain. J. Mol. Biol. 432 : 4466-4480.


Cyt1Aa, one of four crystalline protoxins produced by mosquitocidal bacterium Bacillus thuringiensis israelensis (Bti), forms oligomers that fully perforate and eventually disrupt lipid bilayers. About 35 min after toxin addition, membrane perforation is observed at the periphery of membrane-bound aggregates. The depth of holes can reach 4.5 nm, consistent with a full spanning of the lipid bilayer.
AFM imaging of Cyt1Aa crystals, provided by Guillaume Tetreau, as well as the interaction between Cyt1Aa and lipid bilayers were performed by Jean-Marie Teulon.

Tetreau G, et al. (2020) Serial femtosecond crystallography drives elucidation of mosquitocidal Cyt1Aa bioactivation cascade, from in vivo crystallization to cell lysis. Nat. Comm. 11 : 1153.


The proton pump transmembrane protein bacteriorhodopsin was successfully incorporated into planar floating lipid bilayers in gel and fluid phases, by applying a detergent-mediated incorporation method. The method was optimized on single supported bilayers by using quartz crystal microbalance, atomic force and fluorescence microscopy techniques. Lipid bilayer integrity and protein activity were preserved upon the reconstitution process. Reversible structural modifications of the membrane, induced by the bacteriorhodopsin functional activity triggered by visible light, were observed and characterized at the nanoscale.
AFM imaging was produced by Jean-Marie Teulon with samples prepared by Tetiana Mukhina.

Mukhina T, et al. (2021) Insertion and activation of functional Bacteriorhodopsin in a floating bilayer. J. Colloid Interface Sci. 597 : 370-382.