Quasi-living therapeutics: biomimetic vesicles for bacterial endocytosis

Group Rodriguez-Emmenegger Lab and Nanoprobes and nanoswitches
Group leader: César Rodriguez-Emmenegger (rodriguez@dwi.rwth-aachen) and Marina I. Giannotti (migiannotti@ibecbarcelona.eu)

Research project

The goal of this project is to develop a new concept for antimicrobials based on synthetic cells capable of selectively endocytocing living pathogens. This concept offers the complete separation of the killed bacteria from the environment, preventing the release of cytotoxic endotoxins. We inspire in bacterial endocytosis, a fundamental defensive mechanism of cells. Endocytic pathways share a common physical principle: the binding of the object to preorganized receptors induces an inward-directed force that overcomes the bending rigidity of the membrane causing a change in curvature and engulfment. We will design biomimetic vesicles using synthetic amphiphilic molecules that self-assemble into curved membranes and are able to endocytize bacteria based on natural cells mechanism.

We aim to unveil the minimal requirements for selective endocytosis of bacteria, the basis for the design of therapeutic materials that can engulf pathogens. For selective artificial endocytosis it is decisive that the vesicles display superior stability than conventional liposomes, without losing properties and functionalities such as membrane thickness, flexibility, and lateral mobility. Selective engulfment demands stickers (receptors) that bind weakly but specifically to bacteria. We wish to control the density of receptors while keeping leaflet asymmetry and 2D-segregation in domains. The synergy of binding and bending mechanisms is expected to result in multistability states and pathways with enhanced rate for endocytosis.

We will build and characterize the vesicles including specific receptors for bacteria. We will probe the membrane physical properties relevant to engulfment: i.e. bending rigidity, thickness, lateral mobility and adhesion energy. We will use atomic force microscopy-force spectroscopy surface plasmon resonance, fluctuation analysis, synchrotron X-Ray techniques, to assess membrane’s topography, phase state and domain distribution, nanomechanics and binding affinities.

Job position description

We seek for a candidate with a background in biophysics, physical-chemistry, nanoscience, physics, or related, for an interdisciplinary work. The candidate will work on the design of biomimetic vesicles, the biophysical characterization of the vesicles and of supported membranes, including the phase behavior, meso- and nano-scale structure, nanomechanics using atomic force microscopy and spectroscopy. The candidate will also perform fluctuation analysis, binding affinity assays with surface plasmon resonance (SPR) and atomic force microscopy (AFM)-single molecule force spectroscopy. Structural characterization of membranes will also be complemented with synchrotron X-Ray diffraction and reflectivity on individual membranes in liquid environment. He/she will receive the necessary training for the mentioned techniques and will develop the experimental work in the facilities of IBEC, at the “Bioinspired interactive materials and protocellular systems” (to be established in 2022) and the “Nanoprobes & Nanoswitches” groups. In addition, the PhD will benefit of the training environment of IBEC, institution that is strongly devoted training researchers from the undergraduate up to postdoctoral level.