Mail Address: Department of chemistry,
Université de Montréal,
Postal Box 6128, Station Centre-ville, M Montréal, Québec (Canada) H3C 3J7
Street Address: Department of chemistry,
Université de Montréal,
J.-A.-Bombardier Building, Room 3029
2900, Édouard-Montpetit blvd.,
Montréal, Québec (Canada) H3T 1J4
Telephone: (514) 340-3205 Fax: (514) 343-7586
Electronic mail: firstname.lastname@example.org
Our research program aims at gaining a better understanding and control of the structures and functions of lipid self-assemblies using various spectroscopic techniques including vibrational spectroscopy, solid-state NMR, and fluorescence. Three systems are specifically investigated.
LIPID – PROTEIN/PEPTIDE INTERACTIONS:
Some peptides and some proteins can induce lipid efflux from which results the formation of lipid/protein or peptide self-assemblies. This phenomenon plays important roles in several biological processes. For example, proteins of the bovine seminal plasma interact with sperm membranes from which they extract selectively phosphatidylcholines and cholesterol. This step is essential for sperm maturation. Similarly, ApoA-I and some related peptides have been shown to lead to the formation of small lipidic particles, a phenomenon associated with the control of atherosclerosis. Despite the prime importance of the lipid efflux, the related mechanisms are not detailed from a molecular point of view. We characterize detergent-, peptide- or protein-induced lipid extraction of some key systems with an overall approach, looking at the process from the association to lipid structures to the resulting mixed complexes. The lipid specificity of these processes is often of prime importance (e.g. change of the lipid composition of sperm membranes, reverse cholesterol transport) and we specifically address this aspect by defining the chemical and physical parameters dictating the extraction of specific lipids.
The lipids of the stratum corneum (SC), the top layer of the epidermis, are largely responsible for the skin impermeability. It is believed that this exceptional barrier is linked to the unusual crystalline phase formed by a significant proportion of its lipids. We work on lipid systems mimicking the SC in order to define the parameters dictating the self-organization. Very recently, studying model mixtures that are more complex and, therefore, reproducing quite faithfully the behavior of native SC, we discovered that the resulting structure includes hydrocarbon nanodrops, a phenomenon that leads to reconsider our understanding of the structure/function of SC. We continue to examine the structure and the dynamics of SC models to identify the molecular parameters required for the formation of this unique solid/liquid matrix and to assess its role in skin impermeability. The resulting improved understanding of lipid self-assembly will contribute to maintaining a healthy skin barrier, and potentially to altering the barrier for transdermal drug delivery.
NON PHOSPHOLIPIDIC LIPOSOMES:
We contribute to the use of liposomes for drug targeting. First, we develop a novel family of non phospholipid liposomes formed with a monoalkylated amphiphile and a sterol. Because of their unusually high sterol content, these liposomes display some distinct properties including a very low permeability and a very good stability in harsh milieus. In the next granting period, we propose to push further the development of these novel nanovectors. We develop these nanovectors in order to craft a fine control of the drug release, using a stimulus (e.g. a change of pH, with light). We explore the possibility of functionalizing the surface of the liposomes in order to improve their therapeutic targeting. We believe that the combination of the exceptional impermeability, a controlled stimulus response, and a smart surface grants an interesting potential for these non phospholipid cholesterol-rich liposomes. Second, we collaborate to the project aiming at using nanorobots for active drug targeting, a multidisciplinary project led by Prof. Sylvain Martel, École Polytechnique. In this project, a drug is trapped into liposomes that are subsequently attached to magnetotactic bacteria (i.e. that swim following magnetic field lines). These bacteria are injected near a tumour and then directed towards the core of malignant tissue with magnetic field gradients. As a consequence, the drug is released deep in the tumour and the therapeutic gains are huge.
The investigations of the chemistry of these biological systems are integrated in a multidisciplinary approach ensured by a network of excellent collaborators in physics, microbiology, dermatology, physiology, and pharmacy. We exploit state-of-the-art techniques mainly based on solid-state nuclear magnetic resonance, vibrationnal spectroscopy and microcalorimetry. We have current access state-of-the-art equipment.
More details about the instrumental infrastructures are available on the site of Laboratoire de caractérisation des matériaux (LCM)
The group is presently looking for motivated graduate students.