Nanomaterial interactions with biomembranes: Bridging the gap between soft matter models and biological context

Abstract

Synthetic polymers, nanoparticles, and carbon-based materials have great potential in applications including drug delivery, gene transfection, in vitro and in vivo imaging, and the alteration of biological function. Nature and humans use different design strategies to create nanomaterials: biological objects have emerged from billions of years of evolution and from adaptation to their environment resulting in high levels of structural complexity; in contrast, synthetic nanomaterials result from minimalistic but controlled design options limited by the authors' current understanding of the biological world. This conceptual mismatch makes it challenging to create synthetic nanomaterials that possess desired functions in biological media. In many biologically relevant applications, nanomaterials must enter the cell interior to perform their functions. An essential transport barrier is the cell-protecting plasma membrane and hence the understanding of its interaction with nanomaterials is a fundamental task in biotechnology. The authors present open questions in the field of nanomaterial interactions with biological membranes, including: how physical mechanisms and molecular forces acting at the nanoscale restrict or inspire design options; which levels of complexity to include next in computational and experimental models to describe how nanomaterials cross barriers via passive or active processes; and how the biological media and protein corona interfere with nanomaterial functionality. In this Perspective, the authors address these questions with the aim of offering guidelines for the development of next-generation nanomaterials that function in biological media.

Smart Nanoparticles for Drug Delivery Application: Development of Versatile Nanocarrier Platforms in Biotechnology and Nanomedicine

“…However, despite the remarkable developments of recent methodologies, most of all nanocarriers' action is associated with a number of unwanted side effects that diminish their efficient use in nanomedicine. This highlights some critical issues in the design and engineering of nanocarrier systems for biotechnology applications, arising from the complex environment and multiform interactions established within the specific biological media [6][7][8].…”

Mechanomodulation of Lipid Membranes by Weakly Aggregating Silver Nanoparticles

“…A similar behaviour has been recently reported by Montis et al who showed that cationic AuNPs induce more drastic effects on zwitterionic and negatively charged membranes than anionic and PEG-coated AuNPs 25 . Moreover, the properties of the surrounding medium, such as pH, temperature, ionic strength, macromolecular crowding, and viscosity can modify many important characteristics of NPs such as surface charge, solubility and colloidal stability, and also can modulate their biological activity 21,26,27 . The considerably large number of parameters influencing the NP behaviour along with the complexity of biological membranes, makes the understanding of NP-membrane interactions very challenging.…”

The aggregation of striped nanoparticles in mixed phospholipid bilayers

“…The development of novel mechanisms for the delivery of drugs to biological cells has been the subject of intense study in recent years [1][2][3][4][5][6] . For small drug molecules the main barrier to efficient delivery is typically the cell membrane lipids 7,8 .…”

“…NPs have demonstrated a level of effectiveness through multiple applications in targeted therapy 5,11,12 . However, there are open questions regarding the physical mechanism of how NPs interact with cell membranes, notably the role of the local diversity in the membrane itself and within the cytoplasm of the cell interior 6,10 . For example, phospholipid molecules affect the assembly of the bilayer due to the varying degrees of saturation of the tailgroups, variations in tail length, and/or changes in headgroup functionality.…”