Curso
de posgrado “Monocapas lipídicas como modelo de membrana biológica”
en contexto de la
Red CYTED-BIOTOX, Toxinas de interés para la
Biomedicina,
desarrollado
en el INIBIOLP, La Plata el 25 y 26 de abril del 2013.
domingo, 25 de agosto de 2013
XLI REUNION ANUAL DE LA SOCIEDAD ARGENTINA DE BIOFISICA_Mottola
XLI REUNION ANUAL
DE LA SOCIEDAD ARGENTINA DE BIOFISICA
Surface insertion of
ascorbyl palmitate in phospholipid monolayers
Maria
Laura Fanani*1, Milagro Mottola1, Natalia
Wilke1, Luciano Benedini2 y Bruno Maggio1
(1)
Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC - CONICET).
Depto. Química Biológica, Fac. Ciencias Químicas, Univ. Nac. Córdoba, Córdoba. (2)
Instituto de Química del Sur (INQUISUR – CONICET). Depto. Química, Univ. Nacional del
Sur, Bahía Blanca. *lfanani@fcq.unc.edu.ar
Ascorbyl
palmitate (ASC16) is a molecule of potential pharmacological interest due to
its antioxidant properties and amphiphilic nature. In this work we investigated
its interaction with model lipid monolayers. ASC16 shows an ionizable OH group
(pKa 4.2) that leads to a charged surface upon its insertion/adsorption to
interface (1). When ASC16 is
added to the subfase of a phospholipid monolayer it incorporates to the film
showing a non-classical bimodal kinetics. From the analysis of mixed Langmuir
films and Brewster angle microscopy we can conclude that the insertion kinetics
of ASC16 leads to a two-dimensional phase transition from liquid-expanded
(phospholipid-reach) film to a liquid-condensed phase enriched in the
amphiphilic drug. The latter phase is highly stable at the interface reaching
surface pressure values of ~65mN/m and a
theoretical cut off value near 70mN/m. Subphase pH and ionic strength are
determinant of both the features of ASC16 aggregates in the bulk phase and of the
kinetic properties of ASC16 insertion in phospholipid monolayers. Those effects
are due to different biophysical properties of the drug in its charged and
neutral states. Additionally, we evaluated the insertion of ASC16 in
phospholipid/cholesterol monolayers. In this condition the kinetic of insertion
shows a fast hyperbolic increase. Preliminary results suggest that the presence
of cholesterol disrupts the ASC16-enriched liquid-condensed phase promoting a
rapid ASC16 insertion in the membrane.
References: (1). Benedini, L.,
Fanani, M. L., Maggio, B., Wilke, N., Messina, P., Palma, S., and Schulz, P.
(2011) Langmuir 27, 10914-10919
Aknoledgments: This work was
supported by CONICET, FONCyT, SECyT-UNC. MLF, NW and BM are career researchers
of CONICET.
Simposo Satélite: Toxinas de Interés para la Biomedicina
XLI REUNION ANUAL
DE LA SOCIEDAD ARGENTINA DE BIOFISICA
Simposo Satélite: Toxinas de Interés para la Biomedicina (BIOTOX). Auspiciado por CYTED.
María
Laura Fanani and Bruno Maggio
Centro
de Investigaciones en Química Biológica de Córdoba (CIQUIBIC - CONICET). Depto.
Química Biológica, Fac. Ciencias Químicas, Univ. Nacional de Córdoba, Córdoba.
Sphingomyelinase
(SMase) is a phospholipase that hydrolyzes sphingomyelin producing ceramide,
which remains in the membrane, and the water-soluble phosphocholine. It is
present in bacterial hemolytic cocktails, spider venoms and has an important
role in mammalian cell signal transduction. The production of ceramide induces
important changes in the physical organization of the membrane, which is
proposed as its main biological function. In cholesterol-poor membranes the
enzymatically produced ceramide laterally segregates forming condensed ceramide-enriched
domains (1) whose
composition and morphology depends on the kinetics of ceramida production (2). On the other
hand, in cholesterol-rich membranes the produced ceramide partitions
preferentially in cholesterol-rich liquid-ordered domains, freeing the more
expanded (SMase-rich) active phase from product and allowing the liquid-ordered
domains to act as substrate reservoir. As a consequence SMase shows an enhanced
activity when acting in a membrane that exhibit the coexistence of
liquid-expanded/ liquid-ordered phases (3) compared to
fully liquid-expanded or fully liquid-ordered phases. Therefore, lipid
diffusion and preferential partitioning in the different phases determine the
membrane reactivity, dynamics and bi-dimensional structure that are relevant
for the enzymatic function.
References:
1)
Fanani,
M. L., Hartel, S., Maggio, B., De, T. L., Jara, J., Olmos, F., and Oliveira, R.
G. (2010) Biochim. Biophys Acta 1798, 1309-1323.
2)
Fanani,
M. L., De, T. L., Hartel, S., Jara, J., and Maggio, B. (2009) Biophys. J. 96,
67-76
3)
Ale,
E. C., Maggio, B., and Fanani, M. L. (2012) Biochim Biophys Acta 1818,
2767-2776
Acknoledgments:
This work was supported by CONICET, FONCyT; SECyT-UNC. MLF and BM are career
researchers of CONICET.
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