Physical Society Colloquium

Single nanoparticle analytics:
from viruses via exosomes to drug carriers

Fredrik Höök

Department of Applied Physics
Chalmers University of Technology

Next generation drug-delivery vehicles aimed to carry biological drugs, such as proteins or nucleic acids, are often designed to mimic how natural biological nanoparticles, such as viruses and exosomes, transfer genetic information between cells in vivo. Due to the large heterogeneity of nanoparticles irrespective of whether they are of biological or artificial origin, it is crucially important to advance analytical instrumentation to complement ensemble averaging methods with single nanoparticle analytical approaches[1]. A large set of tools with single-nanoparticle sensitivity is now available, to which we recently contributed a concept that enables simultaneous fluorescent and scattering-based label-free imaging of surface-bound biological nanoparticles [2]. Examples will be shown that illustrate the use of this scattering microscopy concept i) to investigate supported lipid bilayer formation, ii) for label-free measurements of protein binding to individual liposomes, iii) to characterize DLVO-controlled non- specific interactions at cell-membrane mimics,[3] and detergent free enrichment of pre-defined membrane proteins in crude cell membranes.[4] By using a two dimensional fluid supported lipid bilayer, to which biological nanoparticles are directly anchored and imaged, we have also developed a new means to simultaneously determine both nanoparticle size and fluorescence / scattering intensity,[5] which may potentially offer flow-cytometry-like sorting based on distinct features of individual nanoparticles. This 2D flow nanometry concept can alos be used to quantify the valancy of nanoparticle binding to cell-membrane mimics.[6] These new analytical possibilities will be discussed in the context of improved characterization of individual biological nanoparticles of diagnostic and therapeutic significance.

References:
[1] Grandin, H. M., Guillaume-Gentil, O., Zambelli, T., Mayer, M., Houghtaling, J., Palivan, C. G., Textor, M., Hook, F., Bioinspired, nanoscale approaches in contemporary bioanalytics. Biointerphases 2018, 13 (4).
[2] Agnarsson, B., Lundgren, A., Gunnarsson, A., Rabe, M., Kunze, A., Mapar, M., Simonsson, L., Bally, M., Zhdanov, V. P., Hook, F., Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells. ACS Nano 2015, 9 (12), 11849- 62.
[3] Lundgren, A., Agnarsson, B., Zirbs, R., Zhdanov, V. P., Reimhult, E., Hook, F., Nonspecific Colloidal-Type Interaction Explains Size-Dependent Specific Binding of Membrane-Targeted Nanoparticles. ACS Nano 2016, 10 (11), 9974-9982.
[4] Lundgren, A., Fast, B. J., Block, S., Agnarsson, B., Reimhult, E., Gunnarsson, A., Hook, F., Affinity Purification and Single-Molecule Analysis of Integral Membrane Proteins from Crude Cell- Membrane Preparations. Nano Letters 2018, 18 (1), 381-385.
[5] Block, S., Fast, B. J., Lundgren, A., Zhdanov, V. P., Hook, F., Two-dimensional flow nanometry of biological nanoparticles for accurate determination of their size and emission intensity. Nat Commun 2016, 7, 12956.
[6] Block, S., Zhdanov, V. P., Hook, F., Quantification of Multivalent Interactions by Tracking Single Biological Nanoparticle Mobility on a Lipid Membrane. Nano Letters 2016, 16 (7), 4382-4390.