Contact Deformation of Liposome in the Presence of Osmosis JI-JINN FOO, 1 VINCENT CHAN, 1 and KUO-KANG LIU 2 1 Tissue Engineering Laboratory, School of Mechanical and Production Engineering, Nanyang Technological University, Singapore 639798 and 2 Institute of Science and Technology in Medicine, School of Medicine, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent ST4 7QB, United Kingdom (Received 2 January 2003; accepted 5 August 2003) Abstract—The role of osmotic pressure on the geometry of adherent liposome remains an intricate question in the mechan- ics of supramolecular structures. In this study, confocal reflec- tion interference contrast microscopy in combination with cross-polarized microscopy was applied to probe the geometry of deformed liposome on fused silica substrates through the determination of a vesicle–substrate separation profile. In par- allel, a theoretical model which describes the large deformation of the lipid bilayer membrane under both out-plane bending and in-plane shear forces is developed. Then, the global defor- mation geometry of the adherent liposome is rigorously com- pared with our experimental data. It is shown that the adhesion contact area increases in dimension, the liposome volume de- creases, and the vesicle height decreases under the reduced osmotic pressure. The coupling of experimental data and a modified theoretical framework of the adherent liposome pro- vides a more explicit result in comparison with previous studies and demonstrates the possibility of modeling the change of liposome mechanics under the influence of osmosis. © 2003 Biomedical Engineering Society. @DOI: 10.1114/1.1616934# Keywords—Liposome mechanics, Osmotic pressure, Contact area, Membrane bending modulus. INTRODUCTION Cell–substrate interaction plays a prominent role in many physiological functions and pathological processes. 7,16,19 A better understanding of the complex mechanisms involved in cell–substrate adhesion and membrane fusion are crucial for the designs of targeted drug delivery systems and cell therapeutic devices. 17 Thus, the fundamental understanding of the complex ad- hesion mechanism is critical for biomedical research. Several physiochemical parameters such as osmotic pres- sure, temperature, and ionic strength are shown to modu- late the contact mechanism and adhesion energy of ad- herent cell and liposome. 2 Therefore, it is meaningful to quantitatively correlate the contact mechanics of adherent vesicle with the physiochemical driving forces involved in biological adhesion. Currently, there is a lack of uni- fied experimental–theoretical approaches in studying the change of liposome geometry induced by major physio- chemical factors such as the osmotic effect; which is an important mechanism that may modulate cell–substrate adhesion. The effect of osmotic pressure on biomembrane adhe- sion was extensively investigated by Servuss and Hel- frich and Evans. 5,22 Although several experimental stud- ies in liposome adhesion were reported in the literature, a high resolution contour map of liposome–substrate separation and a mathematical model describing the geo- metric transformation of adherent liposome are not cur- rently available. Our group has recently postulated that a thin-walled vesicle adhering on a rigid substrate adopts the shape of a truncated sphere under a stretching domi- nant regime. 11,24 Moreover, Seifert and Seifert and Lip- owsky proposed several geometries of adherent vesicles when the bending effect dominates. 20,21 Pamplona and Calladine developed a theoretical model that couples the stretching and bending effects for modeling the pressure- induced deformation of free-suspended vesicles in aque- ous medium. 14 In their study, a large deformation theory is formulated in terms of several unknown membrane parameters. Parker and Winlove further extended the Pamplona and Calladine model to study the deformation of suspended vesicles under the influence of external forces. 15 Confocal reflection interference contrast microscopy ~C-RICM! was shown to improve the upper limit of the experimental membrane–substrate separation ~up to 4.5 mm! and increase the dynamic range of the probed con- tact zone for adhering capsules on a glass substrate. 12 Simultaneously, cross-polarized light microscopy was ap- plied to measure the midplane diameter of the adherent capsule in order to determine the degree of deformation in our truncated sphere model. 2,6 In this study, we induce a hypertonic condition to adherent vesicles by evaporat- ing water from the surrounding aqueous medium with high power illumination. C-RICM and cross-polarized light microscopy were then applied to elucidate the in- Address correspondence to K. K. Liu, Institute of Science and Technology in Medicine, School of Medicine, Thornburrow Drive, Hartshill, Stoke-on-Trent ST4 7QB, U.K. Electronic mail: i.k.liu@keele.ac.uk; mkkliu@ntu.edu.sg Annals of Biomedical Engineering, Vol. 31, pp. 1279–1286, 2003 0090-6964/2003/31~10!/1279/8/$20.00 Printed in the USA. All rights reserved. Copyright © 2003 Biomedical Engineering Society 1279