Compressibility of Multicomponent, Charged Model Biomembranes Tunes Permeation of Cationic Nanoparticles

Abstract

Cells respond to external stress by altering their membrane lipid composition to maintain fluidity, integrity and net charge. However, in interactions with charged nanoparticles (NPs), altering membrane charge could adversely affect its ability to transport ions across the cell membrane. Hence, it is important to understand possible pathways by which cells could alter zwitterionic lipid composition to respond to NPs without compromising membrane integrity and charge. Here, we report in situ synchrotron X-ray reflectivity (XR) measurements to monitor the interaction of cationic NPs in the form of quantum dots, with phase-separated supported lipid bilayers of different compositions containing an anionic lipid and zwitterionic lipids having variable degrees of stiffness. We observe that the extent of NP penetration into the respective membranes, as estimated from XR data analysis, is inversely related to membrane compression moduli, which was tuned by altering the stiffness of the zwitterionic lipid component. For a particular membrane composition with a discernible height difference between ordered and disordered phases, we were able to observe subtle correlations between the extent of charge on the NPs and the specificity to bind to the charged and ordered phase, contrary to that observed earlier for phase-separated model biomembranes containing no charged lipids. Our results provide microscopic insight into the role of membrane rigidity and electrostatics in determining membrane permeation. This can lead to great potential benefits in rational designing of NPs for bioimaging and drug delivery applications as well as in assessing and alleviating cytotoxicity of NPs.

Spontaneous unbinding transition of nanoparticles adsorbing onto biomembranes: interplay of electrostatics and crowding

“…Consequently, there arises a need for greater energy to trigger the unbinding transition through membrane bending. As mentioned earlier, the unbinding of CQDs from the O1G1 membrane was also independently observed in a separate study by us 44 involving SLBs as the membrane model, thus confirming that the unbinding phenomenon observed here is a robust result irrespective of the structure of the membrane model. The schematic in Fig.…”

“…The unbinding transition of NPs was also associated with a corresponding loss of lipids, suggesting a cooperative process underlying the transition. Our recent studies 44–49 also seem to suggest similar NP concentration-dependent mammalian model bilayer membrane disruption and lipid–NP complex formation on the membrane surface.…”

“…13,33,34 While most of these studies involved the use of single-component lipid membranes, 25,26,[35][36][37][38][39] some reports by us 40 and others 20,34,41,42 considered multi-component systems to observe the interplay of the different parameters that contribute to the binding phenomenon. In our recent work, we observed that fluid-like two-component lipid membranes 43,44 were disrupted to a larger extent by cationic quantum dots (CQDs) as compared to more ordered membranes. It was also observed that these CQDs had a higher binding affinity to the membrane (with one of the lipid components as negatively charged) that had higher packing and, hence, higher charge density.…”

Domain-selective disruption and compression of phase-separated lipid vesicles by amphiphilic Janus nanoparticles

“…Preferential association of NPs with specific membrane domains is known to depend on the surface chemistry of NPs 49 and the mechanical properties of the membrane domains. 50 Previous atomistic simulations have shown that amphiphilic Janus NPs preferentially insert into Ld membrane domains that have less stringent packing constraints compared to Lo domains. 18 In contrast, our study reveals Janus NP-membrane interactions on a significantly larger length scale by examining the collective membrane compression effect of multiple Janus NPs on micron-sized vesicle membranes.…”

Poly(maleic anhydride) Shell Modified with Negatively and Positively Charged Groups to Control Zeta Potential and Hydrodynamic Size of Encapsulated Quantum Dots at Variable pH

“…The encapsulation technique makes it possible to create NCs with the same hydrophobic-polymeric shell and tune physical-chemical properties by controlling various functional group ratios on the surface. The following charged groups can provide a particular surface change and colloidal stability of QDs in aqueous media: carboxyl; [10][11][12][13][14][15][16][17][18][19] phosphate; [13,20] carboxybetaine/mixture of quaternary ammonia and carboxyl; [12,14] sulfobetaine; [12,17,21,22] primary, [15,23,24] secondary, [25] tertiary, [18] and quaternary ammonium. [14,19,26] The corresponding physicalchemical characteristic of QDs modified with the abovementioned surface groups are summarized in Table 1.…”