Previous and current research

The central nervous system (CNS) is a dense, layered 3D interconnected network of neuronal cells, where every neuron makes thousands of specific connections with nearby and remote cognate partners. This ordered architecture provides the proper orientation of synaptic connections that are essential for information processing. Any perturbation of this intricate wiring results in neurological disorders. Understanding the functional connections between cells within a complex network and the underlying molecular recognition is essential for the development of therapeutic strategies.

Mature neurons are highly differentiated cells with hundreds of thin processes spanning hundreds of microns-squared. Any attempt to dissociate neurons from their support tears away the processes and often kills the cells confining neurons to the initial support they were seeded on following isolation from tissue. The lack of tools to manipulate neuron contact has limited fundamental studies of the neuronal synapse formation, as well as cell replacement therapy. Moreover, despite recent advances in tissue engineering, none of the biomaterials currently available are capable of supporting neuronal branching in 3D confining in vitro neuronal network to low neuron density, low connectivity systems.

Our group focus is to integrate advances from chemistry, molecular biology and physics to develop model systems adapted to study neuron-neuron interaction from the molecular interactions that mediate target cell recognition, to the study of neuronal network formation and plasticity in 3D.

To decipher the biophysics of neuron-neuron interactions we have developed surrogate systems that enable us to dissect the molecular interaction involve in the synapse formation in a synthetic system. These hybrid systems allow the use of advanced microscopy techniques to characterize membrane protein interactions and to relate them to the real-time ensemble redistribution of proteins at native neuro-neuronal contacts.

To study neuronal connectivity we have developed a method for culturing neurons that allow controlled encounters between fully differentiated neurons in 3D. This unique approach allows for the transfer of differentiated neurons between culture vessels without detaching them from surfaces or injuring their fine processes. This approach leads to the formation of neuronal network that resemble in vivo network and enable testing of new strategies for cell replacement therapy for neurons.

Future prospects and goals

• Single molecule spectroscopy to decipher the nature and the molecular origin of receptor–ligand interactions involved in cell recognition.

• Engineering biomaterials to support neuronal cell growth and differentiation for cell replacement therapy.

• Study of neuronal network organization plasticity and aging using controlled assembly of 3D neuronal network.

Group Members

List of group members

Selected Publications

Sophie Pautot, Claire Wyart, Ehud Y. Isacoff. “Colloid-guided assembly of oriented 3D neuronal networks.” Nature Methods 5, p. 735-740 (2008)

Sophie Pautot, Hanson Lee, Ehud Y. Isacoff, and Jay T. Groves, “Molecular adhesion of the neuronal synapse reconstituted between live cells and supported lipid bilayers.” Nature Chemical Biology 1, p. 283-289 (2005).

Michael M. Baksh, Camin Dean, Sophie Pautot, Shannon DeMaria, Ehud  Isacoff, Jay T. Groves “Neuronal Activation by GPI-linked Neuroligin-1 Displayed in Synthetic Lipid Bilayer Membranes.” Langmuir, 21,  p.10693-10698 (2005).

Sophie Pautot, B. J. Frisken, Ji-Xin Cheng, Sunney Xie and D.A. Weitz, “Spontaneous formation of lipid structure at the Oil/Water/Lipid interface” Langmuir 19, 10281-10287 (2003).

Sophie Pautot, B. J. Frisken and D.A. Weitz, “Engineering asymmetric vesicles”, Proceedings of the National Academy of Sciences 100, p. 10718-10721 (2003).

Ji-Xin Cheng, Sophie Pautot, D.A. Weitz, and Sunney Xie, ‚“Ordering of Water Molecules between Phospholipid Bilayers Visualized by CARS Microscopy” Proceedings of the National Academy of Sciences 100, p. 9826-9830 (2003).

Sophie Pautot, B. J. Frisken and D.A. Weitz, “Production of unilamellar vesicles using an inverted emulsion”, Langmuir, 19, 2870-2879 (2003).