# Virus physics ## expand\_more Viruses are ubiquitous: for every organism, there are multiple viruses that can infect it. Although we know much about the beautiful structures of viruses, and we understand how certain viruses (the ones that are bad for us) infect a cell, we know little about the dynamics of these organisms. We want to understand the life cycle of viruses from a physical point of view. We are particularly interested in understanding how they self-assemble. The video below (part of a [press release](https://www.seas.harvard.edu/news/2015/12/seeing-viruses-in-new-light) from Harvard SEAS) explains some of our recent work on developing optical tools to see viruses: Embed The simplest viruses consist of only of a single molecule of genomic nucleic acid (DNA or RNA) surrounded by a highly-symmetric protective shell composed of many copies of a single protein (the capsid protein). The structures of mature viruses are known in exquisite, atomic-resolution detail, but the mechanisms by which they form remain a mystery. Many viruses spontaneously assemble themselves within the interior of a host cell by self-assembly, a process that is fundamentally random. How do these perfectly-formed, infectious viruses emerge so efficiently from a randomly fluctuating soup of capsid protein and viral genome? And, once formed, how do they release of their genomes in order to initiate an infection? We are addressing these questions by developing optical techniques that allow us to follow individual virus particles, their proteins, and their genomes, in three dimensions and in real time. We use variations on [holographic microscopy](/holographic-microscopy) and elastic light scattering to do fast, sensitive measurements of single viruses as they assemble and disassemble *in vitro*. Elastic scattering is fast, in principle. One can resolve the dynamics to sub-millisecond precision over long periods of time. In practice, however, the background signal from reflected light, dust, or imperfections in the optical path can easily overwhelm the weak scattering from the viruses. Together with collaborators from the Leiden University, Heraeus Quarzglas, the Leibniz Intitute of Photonic Technology, and the Otto Schott Institute of Material Research, we developed a new technique to overcome these experimental limitations, which we call the "fiberscope". Using the fiberscope, we have been able to track individual unlabeled viruses 26 nm in diameter at rates of thousands of measurements per second (see below). These are the smallest viruses to be tracked on sub-millisecond time scales, which are comparable to the time scales for self-assembly. We are currently working on improving our technique to detect single capsid proteins and follow their assembly. For more details, see our paper in [*ACS Nano*](http://dx.doi.org/10.1021/acsnano.5b05646)*.* ![ccmv3-01.png](/sites/g/files/omnuum4256/files/manoharan/files/ccmv3-01.png) Tracking single, unlabeled, freely diffusing CCMV virions. The color bar indicates the signal level compared to the background. Measurements are taken at 2 KHz, a rate comparable to the timescales of self-assembly. ## Publications Download 8 citations download- [BibTeX](/bibcite/export?pager_style=no_pager&number_of_items=30&sort_field=bibcite_year--desc&taxonomy_filters%5Bfield_hwp_c_researchareas%5D%5B0%5D%5Btarget_id%5D=14696&&&format=bibtex) - [EndNote X3 XML](/bibcite/export?pager_style=no_pager&number_of_items=30&sort_field=bibcite_year--desc&taxonomy_filters%5Bfield_hwp_c_researchareas%5D%5B0%5D%5Btarget_id%5D=14696&&&format=endnote8) - [EndNote 7 XML](/bibcite/export?pager_style=no_pager&number_of_items=30&sort_field=bibcite_year--desc&taxonomy_filters%5Bfield_hwp_c_researchareas%5D%5B0%5D%5Btarget_id%5D=14696&&&format=endnote7) - [Endnote tagged](/bibcite/export?pager_style=no_pager&number_of_items=30&sort_field=bibcite_year--desc&taxonomy_filters%5Bfield_hwp_c_researchareas%5D%5B0%5D%5Btarget_id%5D=14696&&&format=tagged) - [Marc](/bibcite/export?pager_style=no_pager&number_of_items=30&sort_field=bibcite_year--desc&taxonomy_filters%5Bfield_hwp_c_researchareas%5D%5B0%5D%5Btarget_id%5D=14696&&&format=marc) - [PubMedId](/bibcite/export?pager_style=no_pager&number_of_items=30&sort_field=bibcite_year--desc&taxonomy_filters%5Bfield_hwp_c_researchareas%5D%5B0%5D%5Btarget_id%5D=14696&&&format=pubmed_id) - [RIS](/bibcite/export?pager_style=no_pager&number_of_items=30&sort_field=bibcite_year--desc&taxonomy_filters%5Bfield_hwp_c_researchareas%5D%5B0%5D%5Btarget_id%5D=14696&&&format=ris) ### 2024 Williams, L. A.; Neophytou, A.; Garmann, R. F.; Chakrabarti, R.; Manoharan, V. N. [Effect of Coat-Protein Concentration on the Self-Assembly of Bacteriophage MS2 Capsids Around RNA](/publications/effect-coat-protein-concentration-self-assembly-bacteriophage-ms2-capsids). *Nanoscale* **2024**. Williams, L. A.; Neophytou, A.; Garmann, R. F.; Chakrabarti, R.; Manoharan, V. N. [Effect of Coat-Protein Concentration on the Self-Assembly of Bacteriophage MS2 Capsids Around RNA](/publications/effect-coat-protein-concentration-self-assembly-bacteriophage-ms2-capsids). *Nanoscale* **2024**. - [ descriptionPublisher's Version](https://pubs.rsc.org/en/content/articlelanding/2024/nr/d3nr03292b/unauth) - [ descriptionPublisher's Version](https://pubs.rsc.org/en/content/articlelanding/2024/nr/d3nr03292b/unauth) ### 2023 Wit, X. M.; Paine, A. W.; Martin, C.; Goldfain, A. M.; Garmann, R. F.; Manoharan, V. N. [Precise Characterization of Nanometer-Scale Systems Using Interferometric Scattering Microscopy and Bayesian Analysis](/publications/precise-characterization-nanometer-scale-systems-using-interferometric). *Applied Optics* **2023**, *62* (27), 7205-7215. Wit, X. M.; Paine, A. W.; Martin, C.; Goldfain, A. M.; Garmann, R. F.; Manoharan, V. N. [Precise Characterization of Nanometer-Scale Systems Using Interferometric Scattering Microscopy and Bayesian Analysis](/publications/precise-characterization-nanometer-scale-systems-using-interferometric). *Applied Optics* **2023**, *62* (27), 7205-7215. - [ descriptionPublisher's Version](https://opg.optica.org/ao/abstract.cfm?uri=ao-62-27-7205) - [ descriptionPublisher's Version](https://opg.optica.org/ao/abstract.cfm?uri=ao-62-27-7205) ### 2022 Garmann, R. F.; Goldfain, A. M.; Tanimoto, C. R.; Beren, C. E.; Vasquez, F. F.; Villareal, D. A.; Knobler, C. M.; Gelbart, W. M.; Manoharan, V. N. [Single-Particle Studies of the Effects of RNA-Protein Interactions on the Self-Assembly of RNA Virus Particles](/publications/single-particle-studies-effects-rna-protein-interactions-self-assembly-rna). *Proceedings of the National Academy of Sciences* **2022**, *119* (39), e2206292119. Garmann, R. F.; Goldfain, A. M.; Tanimoto, C. R.; Beren, C. E.; Vasquez, F. F.; Villareal, D. A.; Knobler, C. M.; Gelbart, W. M.; Manoharan, V. N. [Single-Particle Studies of the Effects of RNA-Protein Interactions on the Self-Assembly of RNA Virus Particles](/publications/single-particle-studies-effects-rna-protein-interactions-self-assembly-rna). *Proceedings of the National Academy of Sciences* **2022**, *119* (39), e2206292119. - [ descriptionPublisher's Version](https://www.pnas.org/doi/abs/10.1073/pnas.2206292119) - [ descriptionPublisher's Version](https://www.pnas.org/doi/abs/10.1073/pnas.2206292119) ### 2020 Forster, R.; Weidlich, S.; Nissen, M.; Wieduwilt, T.; Kolbelke, J.; Goldfain, A. M.; Chiang, T. K.; Garmann, R. F.; Manoharan, V. N.; Lahini, Y.; Schmidt, M. A. [Tracking and Analyzing the Brownian Motion of Nano-Objects Inside Hollow Core Fibers](/publications/tracking-and-analyzing-brownian-motion-nano-objects-inside-hollow-core-fibers). *ACS Sensors* **2020**, *5* (3), 879-886. Forster, R.; Weidlich, S.; Nissen, M.; Wieduwilt, T.; Kolbelke, J.; Goldfain, A. M.; Chiang, T. K.; Garmann, R. F.; Manoharan, V. N.; Lahini, Y.; Schmidt, M. A. [Tracking and Analyzing the Brownian Motion of Nano-Objects Inside Hollow Core Fibers](/publications/tracking-and-analyzing-brownian-motion-nano-objects-inside-hollow-core-fibers). *ACS Sensors* **2020**, *5* (3), 879-886. - [ descriptionPublisher's Version](https://pubs.acs.org/doi/abs/10.1021/acssensors.0c00339) - [ descriptionPublisher's Version](https://pubs.acs.org/doi/abs/10.1021/acssensors.0c00339) ### 2019 Garmann, R. F.; Goldfain, A. M.; Manoharan, V. N. [Measurements of the Self-Assembly Kinetics of Individual Viral Capsids Around Their RNA Genome](/publications/measurements-self-assembly-kinetics-individual-viral-capsids-around-their-rna). *Proceedings of the National Academy of Sciences* **2019**, *116* (45), 22485-22490. Garmann, R. F.; Goldfain, A. M.; Manoharan, V. N. [Measurements of the Self-Assembly Kinetics of Individual Viral Capsids Around Their RNA Genome](/publications/measurements-self-assembly-kinetics-individual-viral-capsids-around-their-rna). *Proceedings of the National Academy of Sciences* **2019**, *116* (45), 22485-22490. - [ descriptionPublisher's Version](https://www.pnas.org/doi/abs/10.1073/pnas.1909223116) - [ descriptionPublisher's Version](https://www.pnas.org/doi/abs/10.1073/pnas.1909223116) ### 2016 Goldfain, A.; Garmann, R.; Jin, Y.; Lahini, Y.; Manoharan, V. N. [Dynamic Measurements of the Position, Orientation, and DNA Content of Individual Unlabeled Bacteriophages](/publications/dynamic-measurements-position-orientation-and-dna-content-individual). *The Journal of Physical Chemistry B* **2016**, *120* (26), 6130–6138. Goldfain, A.; Garmann, R.; Jin, Y.; Lahini, Y.; Manoharan, V. N. [Dynamic Measurements of the Position, Orientation, and DNA Content of Individual Unlabeled Bacteriophages](/publications/dynamic-measurements-position-orientation-and-dna-content-individual). *The Journal of Physical Chemistry B* **2016**, *120* (26), 6130–6138. - add\_circle\_outline do\_not\_disturb\_on Abstract - [ descriptionPublisher's Version](http://dx.doi.org/10.1021/acs.jpcb.6b02153) - [ picture\_as\_pdfGoldfain et al. - 2016 - ...](/sites/g/files/omnuum4256/files/manoharan/files/goldfain_et_al._-_2016_-_dynamic_measurements_of_the_position_orientation_and_dna_content_of_individual_unlabeled_bacteriophages.pdf) A complete understanding of the cellular pathways involved in viral infections will ultimately require a diverse arsenal of experimental techniques, including methods for tracking individual viruses and their interactions with the host. Here we... - [ descriptionPublisher's Version](http://dx.doi.org/10.1021/acs.jpcb.6b02153) - [ picture\_as\_pdfGoldfain et al. - 2016 - ...](/sites/g/files/omnuum4256/files/manoharan/files/goldfain_et_al._-_2016_-_dynamic_measurements_of_the_position_orientation_and_dna_content_of_individual_unlabeled_bacteriophages.pdf) ### 2015 Faez, S.; Latin, Y.; Weidlich, S.; Garmann, R. F.; Wondraczek, K.; Zeisberger, M.; Schmidt, M. A.; Orrit, M.; Manoharan, V. N. [Fast, Label-Free Tracking of Single Viruses and Weakly Scattering Nanoparticles in a Nanofluidic Optical Fiber](/publications/fast-label-free-tracking-single-viruses-and-weakly-scattering-nanoparticles). *ACS Nano* **2015**, *9* (12), 12349-12357. Faez, S.; Latin, Y.; Weidlich, S.; Garmann, R. F.; Wondraczek, K.; Zeisberger, M.; Schmidt, M. A.; Orrit, M.; Manoharan, V. N. [Fast, Label-Free Tracking of Single Viruses and Weakly Scattering Nanoparticles in a Nanofluidic Optical Fiber](/publications/fast-label-free-tracking-single-viruses-and-weakly-scattering-nanoparticles). *ACS Nano* **2015**, *9* (12), 12349-12357. - add\_circle\_outline do\_not\_disturb\_on Abstract - [ descriptionPublisher's Version](http://pubs.acs.org/doi/abs/10.1021/acsnano.5b05646) - [ picture\_as\_pdfFaez et al. - 2015 - Fast...](/sites/g/files/omnuum4256/files/manoharan/files/faez_et_al._-_2015_-_fast_label-free_tracking_of_single_viruses.pdf) High-speed tracking of single particles is a gateway to understanding physical, chemical, and biological processes at the nanoscale. It is also a major experimental challenge, particularly for small, nanometer-scale particles. Although methods such as... - [ descriptionPublisher's Version](http://pubs.acs.org/doi/abs/10.1021/acsnano.5b05646) - [ picture\_as\_pdfFaez et al. - 2015 - Fast...](/sites/g/files/omnuum4256/files/manoharan/files/faez_et_al._-_2015_-_fast_label-free_tracking_of_single_viruses.pdf) Garmann, R. F.; Sportsman, R.; Beren, C.; Manoharan, V. N.; Knobler, C. M.; Gelbart, W. M. [A Simple RNA-DNA Scaffold Templates the Assembly of Monofunctional Virus-Like Particles](/publications/simple-rna-dna-scaffold-templates-assembly-monofunctional-virus-particles). *JACS* **2015**, *137* (24), 7584–7587. Garmann, R. F.; Sportsman, R.; Beren, C.; Manoharan, V. N.; Knobler, C. M.; Gelbart, W. M. [A Simple RNA-DNA Scaffold Templates the Assembly of Monofunctional Virus-Like Particles](/publications/simple-rna-dna-scaffold-templates-assembly-monofunctional-virus-particles). *JACS* **2015**, *137* (24), 7584–7587. - add\_circle\_outline do\_not\_disturb\_on Abstract - [ descriptionPublisher's Version](http://dx.doi.org/10.1021/jacs.5b03770) - [ picture\_as\_pdfGarmann\_JACS\_2015.pdf](/sites/g/files/omnuum4256/files/manoharan/files/garmann_jacs_2015.pdf) Using the components of a particularly well-studied plant virus, cowpea chlorotic mottle virus (CCMV), we demonstrate the synthesis of virus-like particles (VLPs) with one end of the packaged RNA extending out of the capsid and into the surrounding... - [ descriptionPublisher's Version](http://dx.doi.org/10.1021/jacs.5b03770) - [ picture\_as\_pdfGarmann\_JACS\_2015.pdf](/sites/g/files/omnuum4256/files/manoharan/files/garmann_jacs_2015.pdf) ## Project team [### Ben Hafner ](/people/ben-hafner) Ben is an incoming PhD student in applied physics, currently working on in-line holographic microscopy of cyanobacteria. He loves Wikipedia rabbit holes, mechanical clocks, and outdoorsy stuff. ![Ben Hafner headshot](/sites/g/files/omnuum4256/files/styles/hwp_4_5__690x865/public/2025-09/ben.jpg?h=cc11cc1a&itok=KIUr8EZu) [### Francesca Soddu ](/people/francesca-soddu) Graduate Student Francesca is a graduate student in Applied Physics. She studies viral lysis of cyanobacteria. Francesca loves horses and cheese crackers. ![Francesca](/sites/g/files/omnuum4256/files/styles/hwp_4_5__690x865/public/manoharan/files/06ddd635-b00c-42a8-a350-48120c71a76e_1_105_c_1.jpeg?itok=lfpSvMz-) [### Kai Torrens ](/people/kai-torrens) [kai\_torrens@g.harvard.edu](mailto:kai_torrens@g.harvard.edu)PhD Student Kai is a PhD student in Physics studying short-range interactions in colloidal and biological systems. Outside his experiments and calculations, Kai likes board games, going to museums, and walking outside. ![Kai headshot](/sites/g/files/omnuum4256/files/styles/hwp_4_5__690x865/public/2025-01/71079757393__F6305FFA-DC0A-4E93-A64F-EABAB63266F5.jpg?itok=ePoqVI_i) [### Stefania Ketzetzi ](/people/stefania-ketzetzi)Postdoctoral Scholar Stefania is a postdoc studying disassembly of protein complexes and lysis of microbes. Her goal is to understand how tiny living systems destabilize and break apart, thereby laying the groundwork for a theory of biological disassembly. Her background is... ![Stefania](/sites/g/files/omnuum4256/files/styles/hwp_4_5__690x865/public/2025-01/Stefania.jpg?h=bd25a449&itok=_YVeeUfT) ## Alumni [### Ava Williamson ](/people/ava-williamson) [ava\_williamson@g.harvard.edu](mailto:ava_williamson@g.harvard.edu) Ava was a Masters student in the Physics department. She worked on understanding cyanobacterial lysis. Ava is a fan of chocolate treats and hiking - even better if they are together! She earned her Masters degree in 2025. ![Ava](/sites/g/files/omnuum4256/files/styles/hwp_4_5__690x865/public/manoharan/files/img_6456.jpg?itok=mlsD8gV2) [### Julia Harms ](/people/julia-harms) Former visiting undergraduate Julia was a visiting undergraduate researcher who studied phycobilisome dissociation and diffusion in cyanobacteria. Outside of the lab, Julia enjoys very long walks and visual arts. ![Julia headshot](/sites/g/files/omnuum4256/files/styles/hwp_4_5__690x865/public/2025-01/julia.png?h=a8fba58a&itok=kBBCFfl6) [### Yoav Lahini ](/people/yoav-lahini) Former postdoctoral fellow Yoav was a postdoctoral fellow who studied the self-assembly and disassembly dynamics of viruses and the nature of interactions between nanoparticles using ultra-sensitive optical methods. Yoav earned his PhD at the Weizmann Institute of Science in Israel... ![Yoav](/sites/g/files/omnuum4256/files/styles/hwp_4_5__690x865/public/manoharan/files/yoav.jpg?itok=NnA2McC2) See also:- [ Current research areas ](/research-areas/current-research-areas) - [ Virus physics ](/research-areas/virus-physics) - [ Project descriptions ](/page-categories/project-descriptions)