Title: Unveiling Molecular Diffusion in the Brain with Multidimensional Single-Particle Localization Microscopy
Speaker: Prof. Laurent COGNET
Time: 14:00, 22 September (Tuesday)
Location: Room 215, No. 8 Hainayuan Building
Abstract:
Single-molecule localization microscopy (SMLM) has set a new paradigm in optical imaging, providing access to structural and dynamic processes at the nanoscale, well beyond the diffraction limit. Yet, extending SMLM from isolated cells to complex, intact biological tissues remains challenging, notably because of the limited brightness of fluorescent emitters and poor light penetration at visible wavelengths.
To circumvent these limitations, we developed a framework combining SMLM with single-wall carbon nanotubes luminescing in the short-wave infrared (SWIR). Tracking individual nanotubes enables the extracellular space (ECS) of intact live brain tissues to be mapped and explored at the nanoscale, including in the context of neurodegenerative diseases. Building on this strategy, I will present how a toolbox of SWIR nanoprobes, advanced optical modalities, and analytical methods can reveal the complexity of diffusion processes in the brain ECS. Our recent measurements preformed in 3D uncover the scale-dependent emergence of hindered diffusion, providing new insights into the physical organization and transport properties of this complex medium. Finally, single-particle orientation tracking of ultrashort nanotubes allows local viscosity and spatial tortuosity to be disentangled, revealing rheological features inaccessible through translational diffusion analysis alone.
Super-resolved trajectory of a fluorescent carbon nanotube obtained by dynamic localization microscopy, revealing the nanoscale organization of the brain extracellular space and its alterations in pathological conditions. Adapted from A. G. Godin, et al Nat. Nanotechnol. 12 (2017) 238-243 and F. N. Soria et al Nat. Commun. 11 (2020) 3440
3D single-particle tracking of ultrashort carbon nanotubes deep within live mouse brain slices using point-spread-function engineering on a single-molecule microscope. Adapted from Nandi et al ACS Nano 19, 21, (2025) 19818.
Bio：
Laurent COGNET is a Research Director in Physics at CNRS and Principal Investigator in nanoscience and biophotonics.
He is also the director of Laboratoire Photonique Numérique & Nanoscience (LP2N) the joint research Unit of Institut d’Optique Graduate School, CNRS and Univ.Bordeaux.
He received his PhD in quantum physics in 1999 from Université Paris-Saclay under the supervision of Alain Aspect, before moving into nano- and biophotonics as a Marie Curie postdoctoral fellow with Thomas Schmidt at Leiden University (Netherlands). He joined CNRS as a tenured researcher in Bordeaux in 2000 and has been a CNRS Research Director since 2009. In 2006–2007, he was a Fulbright Visiting Scholar at Rice University (Houston TX).
Over the past 25+ years, his research has spanned single-molecule localization microscopy and carbon nanotube nanoscience, bridging nanophysics, biophotonics, and neuroscience. He currently develops innovative single molecule nanoprobes and optical microscopy methods to explore molecular diffusion across a wide range of complex biological environments.
