Welcome
to the
Laboratory
of Biomolecular Self-Assembly Study,
Department
of chemistry,
Université de Montréal
Michel Lafleur,
Full professor,
|
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: michel.lafleur@umontreal.ca
Prof. Michel Lafleur's profile
Member of CQMF - Centre québécois sur les matériaux fonctionnels
REASEARCH
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.
SKIN:
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)
For more information about our group, you can contact Michel Lafleur.
Site of the chemistry department, Université
de Montréal