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Nanoscale optomechanical actuators for controlling mechanotransduction in living cells

Nature Methods volume 13, pages 143–146 (2016)Cite this article

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Abstract

To control receptor tension optically at the cell surface, we developed an approach involving optomechanical actuator nanoparticles that are controlled with near-infrared light. Illumination leads to particle collapse, delivering piconewton forces to specific cell surface receptors with high spatial and temporal resolution. We demonstrate optomechanical actuation by controlling integrin-based focal adhesion formation, cell protrusion and migration, and T cell receptor activation.

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Figure 1: Schematic and characterization of optomechanical actuator (OMA) nanoparticles.
Figure 2: Optomechanical actuation of integrins leads to GFP-paxillin and LifeAct-mCherry recruitment.
Figure 3: Optical control of cell migration and T cell activation by OMA nanoparticles.

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Acknowledgements

The authors are grateful for support from the US National Institutes of Health (R01-GM097399), the Alfred P. Sloan Research Fellowship, the Camille-Dreyfus Teacher-Scholar Award, the National Science Foundation (NSF) EAGER Award (1362113) and the NSF CAREER Award (1350829). This project was supported in part by the Emory University Integrated Cellular Imaging Microscopy Core. We thank M. Zhang for DLS data and S. Nie (Emory University and the Georgia Institute of Technology, Atlanta, Georgia, USA) for instrument access. We thank B. Evavold and L. Blanchfield (Emory University) for pMHC and T cells. We also thank C. Hill (Emory University) for access to the temperature-controlled visible-infrared spectrophotometer.

Author information

Author notes

  1. Zheng Liu and Yang Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, Emory University, Atlanta, Georgia, USA

    Zheng Liu, Yang Liu, Yuan Chang, Kevin Yehl, Yun Zhang & Khalid Salaita

  2. Georgia Institute of Technology, George W. Woodruff School of Mechanical Engineering, Atlanta, Georgia, USA

    Hamid Reza Seyf & Asegun Henry

  3. Georgia Institute of Technology, School of Materials Science and Engineering, Atlanta, Georgia, USA

    Asegun Henry

  4. Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA

    Alexa L Mattheyses

  5. AFM Business Unit, Bruker Nano Surfaces, Santa Barbara, California, USA

    Zhuangqun Huang

Authors
  1. Zheng Liu
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Contributions

K.S. and Z.L. devised the overall experimental strategy. Z.L. and Y.L. performed cell experiments and analyzed data. Z.L. synthesized and characterized the OMAs and developed the near-infrared laser illumination system for investigating the kinetics of OMAs and for single-cell-stimulation experiments. Y.L. synthesized molecular tension sensors. Y.C. and Y.L. synthesized the RGD-N3 molecule. Z.L., Y.L., K.Y. and Y.Z. performed OMA modification. H.R.S. and A.H. performed the thermal simulations. A.L.M., Y.L. and Z.L. performed the 3D-SIM experiments and TIRF nanometry analysis. Z.H. performed temperature-controlled AFM. The manuscript was prepared by Z.L. and K.S. with input from all authors.

Corresponding author

Correspondence to Khalid Salaita.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–20, Supplementary Note and Supplementary Table 1 (PDF 3116 kb)

Time-lapse fluorescence video of the dynamics of OMA nanoparticles during NIR actuation

The OMA particles were labeled with Alexa Fluor 488. The NIR laser was operated at 50% duty cycle at a frequency of 1 Hz. The fluorescence images were acquired using an sCMOS camera at a 0.9 ms frame rate. The experiment was performed in DI water at 37 °C. (AVI 2934 kb)

Time-lapse fluorescence video of a NIH/3T3 cell transfected with GFP-paxillin during NIR actuation

The circle indicates the location of NIR illumination, which was maintained at a 10 Hz frequency, 10% duty cycle, and average power density = 11.3 µW µm−2. The exposure time was 200 msec and the images were acquired at 1 frame/min. (AVI 4898 kb)

Time-lapse fluorescence video of a NIH/3T3 cell transfected with GFP-paxillin and treated with 20 µM ROCK inhibitor 30 min prior to conducting the experiment

The circle indicates the location of NIR illumination, which was identical to the conditions used in Supplementary Movie 2 (10 Hz frequency, 10% duty cycle, and average power density = 11.3 µW µm−2). The exposure time was 200 msec and the images were acquired at 1 frame/min. (AVI 1742 kb)

Time-lapse fluorescence video of a NIH/3T3 transfected with Life-act mcherry during NIR actuation

The circle indicates the location of NIR stimulation. The exposure time was 200 msec and the images were acquired at 1 frame/min. 10 Hz frequency, 10% duty cycle, power density = 11.3 µW µm−2. (AVI 2369 kb)

The cell migrated in response to the location of the NIR illumination

Timelapse fluorescence video of a NIH 3T3 cells transfected with Life-act mcherry. In this video, the pulsed NIR illumination, denoted by the white circle, was moved across the field of view. Over the duration of the video, the cell migrated in response to the location of the NIR illumination. The exposure time was 200 msec and the images were acquired at 1 frame/min. Scale bar: 10µm. The duration of the video was approximately 2 hours. (AVI 68272 kb)

Triggering T cell activation by OMA actuation

Timelapse fura-2 ratio images showing calcium flux of OT-1 T cells following NIR illumination of OVA pMHC decorated OMA nanoparticles. T cells displayed a calcium flux within one minute of NIR illumination. The white circle indicates the location of NIR illumination, which was maintained at a 10 Hz frequency, 10% duty cycle, and average power density = 11.3 µW µm−2. The duration of the video is 12 min and 20 sec. The interval between images was 20 sec. (AVI 29188 kb)

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Liu, Z., Liu, Y., Chang, Y. et al. Nanoscale optomechanical actuators for controlling mechanotransduction in living cells. Nat Methods 13, 143–146 (2016). https://doi.org/10.1038/nmeth.3689

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