Characterization of structures and molecular interactions of RNA and lipid carriers using atomic force microscopy

Jingyi Wang; Jiawen Zhang; Sijia Li; Dengfeng Liu; Akhilesh Bhambhani; Hongbo Zeng

doi:10.1016/j.cis.2023.102855

Characterization of structures and molecular interactions of RNA and lipid carriers using atomic force microscopy

Adv Colloid Interface Sci. 2023 Mar:313:102855. doi: 10.1016/j.cis.2023.102855. Epub 2023 Feb 7.

Authors

Jingyi Wang¹, Jiawen Zhang², Sijia Li³, Dengfeng Liu⁴, Akhilesh Bhambhani⁴, Hongbo Zeng⁵

Affiliations

¹ College of Chemistry and Chemical Engineering, Southwest Petroleum University, Chengdu, Sichuan 610500, China; Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada.
² School of Materials Science and Engineering, Southeast University, Nanjing 211189, China; Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada.
³ Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada.
⁴ Ultragenyx Pharmaceutical Inc., 5000 Marina Blvd, Brisbane, CA 94005, USA.
⁵ Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada. Electronic address: hongbo.zeng@ualberta.ca.

PMID: 36774766
DOI: 10.1016/j.cis.2023.102855

Abstract

Ribonucleic acid (RNA) and lipid are essential biomolecules in many biological processes, and hold a great prospect for biomedical applications, such as gene therapy, vaccines and therapeutic drug delivery. The characterization of morphology and intra-/inter-molecular interactions of RNA and lipid molecules is critical for understanding their functioning mechanisms. Atomic force microscopy (AFM) is a sophisticated technique for characterizing biomolecules featured by its piconewton force sensitivity, sub-nanometer spatial resolution, and flexible operation conditions in both air and liquid. The goal of this review is to highlight the representative and outstanding discoveries of the characterization of RNA and lipid molecules through morphology identification, physicochemical property determination and intermolecular force measurements by AFM. The first section introduces the AFM imaging of RNA molecules to obtain high-resolution morphologies and nanostructures in air and liquid, followed by the discussion of employing AFM force spectroscopy in understanding the nanomechanical properties and intra-/inter-molecular interactions of RNA molecules, including RNA-RNA and RNA-biomolecule interactions. The second section focuses on the studies of lipid and RNA encapsulated in lipid carrier (RNA-lipid) by AFM as well as the sample preparation and factors influencing the morphology and structure of lipid/RNA-lipid complexes. Particularly, the nanomechanical properties of lipid and RNA-lipid characterized by nanomechanical imaging and force measurements are discussed. The future perspectives and remaining challenges on the characterization of RNA and lipid offered by the versatile AFM techniques are also discussed. This review provides useful insights on the characterization of RNA and lipids nanostructures along with their molecular interactions, and also enlightens the application of AFM techniques in investigating a broad variety of biomolecules.

Keywords: Atomic force microscopy; Imaging; Lipid; RNA; Single-molecule force spectroscopy.

Publication types

Review

MeSH terms

Lipids
Mechanical Phenomena
Microscopy, Atomic Force / methods
Nanostructures*
RNA*

Substances

RNA
Lipids