Biomolecules and Biomaterials
Surfactant Effects of Chlorpromazine and Imipramine on Lipid Bilayers Containing Sphingomyelin and Cholesterol

https://doi.org/10.1006/jcis.2002.8690Get rights and content

Abstract

The surface-active drugs chlorpromazine (CPZ) and imipramine (IP) have been tested on large unilamellar vesicles composed of phosphatidylcholine (PC), sphingomyelin (SM), and cholesterol (Ch) in different proportions. The well-characterized nonionic detergent Triton X-100 (TX) has also been used in parallel experiments. Leakage of vesicular aqueous contents and bilayer solubilization have been measured for each surfactant molecule and vesicle composition. All three surface-active molecules behave in a qualitatively similar way, irrespective of bilayer composition: they induce leakage at concentrations well below their critical micellar concentrations (cmc) and solubilization near the cmc. In these events, the potency of the three surfactants under study increases with decreasing cmc, in the order IP<CPZ<TX. With all three surfactant molecules, addition of SM to PC bilayers made the vesicles more sensitive to the detergents. The three surfactants had the same effects on PC : SM (3 : 1 mole ratio) and on PC : SM : Ch (3 : 1 : 1 mole ratio) vesicles when leakage was tested. However, the presence of cholesterol made the bilayers more resistant to solubilization. In the presence of both SM and Ch, CPZ and IP, but not TX, were able to achieve complete bilayer solubilization. Since the outer monolayer of plasma membranes is rich in SM and Ch, the present data could be relevant in understanding some of the CPZ or IP effects at the membrane level.

References (25)

  • S. Schreier et al.

    Biochim. Biophys. Acta

    (2000)
  • F.R. Leterrier et al.

    Biochem. Pharmacol.

    (1974)
  • M. Luxnat et al.

    Biochim. Biophys. Acta

    (1986)
  • C.O. Abernathy et al.

    Biochem. Pharmacol.

    (1975)
  • E. London et al.

    Biochim. Biophys. Acta

    (2000)
  • J. Ruiz et al.

    Biochim. Biophys. Acta

    (1988)
  • L.D. Mayer et al.

    Biochim. Biophys. Acta

    (1986)
  • M.A. Partearroyo et al.

    FEBS Lett.

    (1992)
  • R. Hertz et al.

    J. Colloid Interface Sci.

    (1977)
  • A. Alonso et al.

    FEBS Lett.

    (1981)
  • R. Sáez et al.

    FEBS Lett.

    (1985)
  • A. Helenius et al.

    Biochim. Biophys. Acta

    (1975)
  • Cited by (25)

    • Lipid bilayers: Phase behavior and nanomechanics

      2020, Current Topics in Membranes
      Citation Excerpt :

      These results are in agreement with recent calorimetric studies of free-standing membranes of the same systems (Mannock et al., 2010). The role of Chol in the structure and nanomechanics of SLBs has been extensively studied by AFM (Adhyapak et al., 2018; Al-Rekabi & Contera, 2018; Garcia-Manyes et al., 2010; Redondo-Morata, Giannotti, & Sanz, 2012b; Sullan et al., 2010), as well as its interplay with sphingolipids or other lipids (Ahyayauch et al., 2002; García-Arribas et al., 2016; Guyomarc'h et al., 2014) and further reviewed in Gumí-Audenis et al. (2016). By means of temperature-controlled AFM imaging and AFM-FS to assess the influence of Chol on the membrane ordering and stability (Redondo-Morata, Giannotti, & Sanz, 2012b), this work analyzed a DPPC:Chol in representative range of compositions up to 50 mol% Chol, studying the phase evolution upon heating (from room temperature to temperatures high above the Tm of DPPC) and the corresponding nanomechanical stability.

    • Study of rabbit erythrocytes membrane solubilization by sucrose monomyristate using laurdan and phasor analysis

      2018, Colloids and Surfaces B: Biointerfaces
      Citation Excerpt :

      The actual definition of rafts correspond to structures existing in vivo that are sterol and sphingolipid-enriched, with small size (10–200 nm), heterogeneous and highly dynamic [13]. The solubilization process in bio membranes may be different depending on the state of this structures, in fact, the presence of cholesterol in lipid mixtures makes the bilayers more resistant to solubilization [14], and in equimolar mixtures with phosphatidylcholine, cholesterol decreased the stability of the bilayer towards Triton X-100 [15]. Erythrocytes are the most commonly used model system to study bio membranes due to their relatively simple structure: they lack nuclei and organelles, having only the plasma membrane.

    • The mechanism of detergent solubilization of lipid bilayers

      2013, Biophysical Journal
      Citation Excerpt :

      The available information on the temporal order of these observations and on the dependence of temporal order on the physico-chemical properties and concentrations of the lipid and detergent is quite limited. It is known, however, that solubilization is preceded by leakage of entrapped solutes, as indicated by investigations of permeability at subsolubilizing detergent concentrations (61,62). When solubilization is preceded by a lag, the leakage is slow, assuming that detergent equilibration over the two monolayers is a prerequisite to pore formation and solubilization and thus it appears that solubilization occurs only after the bilayer is perforated (29).

    • Spontaneous vesicles, disks, threadlike and spherical micelles found in the solubilization of DMPC liposomes by the detergent DTAC

      2012, Journal of Colloid and Interface Science
      Citation Excerpt :

      Because bilayer structures (liposomes and disks) were completely solubilized, this D:L range corresponds to stage III of the model [4,5]. Detergents are commonly used for lipid and protein solubilization [41–43], but their study has been mostly limited to obtain critical detergent/lipid ratios at phase boundaries [8,44,45]. Additional work is still required to investigate the effect of detergents on lipids.

    • Accumulated bending energy elicits neutral sphingomyelinase activity in human red blood cells

      2012, Biophysical Journal
      Citation Excerpt :

      Detergents (or surfactants) are known to modify the activity of membrane enzymes in various ways (19,20). As shown in Table 1, surfactants of widely different chemical structures, such as CPZ, Na DOC, and lysoPC (all at concentrations well below their critical micellar concentrations to ensure that they would interact with the membrane in the form of monomers (21)) induced SMase activity in RBCs under isotonic conditions to a similar extent as did hypotonic shock (Table 1). PLA2, which cleaves PC (among other phospholipids) to lysoPC and free fatty acids, also induced SMase activity (Table 1).

    View all citing articles on Scopus
    1

    To whom correspondence should be addressed. Fax: +34-94-464 8500. E-mail: [email protected].

    View full text