Biomolecular plasmonics for quantitative biology and nanomedicine
Introduction
Our understanding of biological systems is increasingly dependent on our ability to visualize and precisely measure the dynamics of molecular, biological, biophysical events with high spatial and temporal resolution, within the context of a living cell. The living cell dynamically responds to its perpetually changing environment, such that signaling proteins, transcription factors, and enzymes are constantly synthesized, transported from one organelle to another, and finally shuttled to their appropriate locations to give rise to cell function. The intracellular distribution of these molecular complexes is spatially non-uniform and dynamically changing over time in response to environmental cues [1]. Quantitative knowledge of the intracellular biochemical distribution is crucial for understanding intracellular organization and function in developmental processes, growth, differentiation, apoptosis, and disease. In this regard, the development of nanoplasmonic optical antennae for cellular and molecular imaging techniques, as well as nanoplasmonic gene switches, are of considerable interest in many areas of research, from molecular and cellular biology to molecular diagnostics to nanomedicine. Label-free nanoplasmonic optical antennae, also referred to as nanomechanical probes, offer multiple advantages over traditional molecular imaging techniques: stability, biocompatibility, selectivity, and spectroscopic imaging capability. By visualization and wireless communication via nanoplasmonic optical antennae within a living cell, we can obtain quantitative spectral snapshots of what we refer to as the intracellular galaxy (Figure 1a).
By focusing on a specific antenna within this intracellular galaxy, we can probe localized biochemical data to explore the living intracellular environment (Figure 1b). Intracellular manipulation in conjunction with real-time imaging can provide unparalleled insight into the dynamic biochemical distribution as a result of local environmental changes. Recent advancements in nanotechnology and nanoplasmonics now enable subnanometer and nanometer tools to directly interface with intracellular processes. By focusing electromagnetic fields down to dimensions smaller than the diffraction limit, nanoplasmonic optical antennae – functioning as nanoplasmonic gene switches – enable spatiotemporally precise regulation of genetic activity to give rise to location-specific function [2••, 3••, 4••]. Nanoplasmonic optical antennae – functioning as biosensors – also focus electromagnetic fields to significantly enhance spectral information for plasmon resonance energy transfer (PRET) [5••, 6••, 7••], surface-enhanced Raman spectroscopy (SERS) [8, 9, 10, 11, 12, 13, 14, 15, 16], nanoplasmonic molecular rulers [17••], and integrated photoacoustic–photothermal contrast agents [18••]. In this way, quantitative spectral snapshots of the intracellular biochemical distribution can be obtained over time as function of changes in the local environment. In this review, the dual functions of nanoplasmonic optical antennae, as nanoplasmonic gene switches and biosensors, for quantitative biology and nanomedicine, are discussed (Figure 2).
Section snippets
Dual functions of nanoplasmonic optical antennae
Dual-functional nanoplasmonic optical antennae are powerful biological tools for on-demand gene regulation and label-free biosensing. A nanoplasmonic optical antenna receives, focuses, and transmits incoming optical and near-infrared (NIR) electromagnetic radiation as an analogous, classical antenna receives, focuses, and transmits radio-frequency electromagnetic radiation. A nanoplasmonic optical antenna focuses incoming electromagnetic radiation down to dimensions smaller than the diffraction
Nanocrescent antennae for SERS
For biological and biomedical applications, the ideal biologically functional nanoplasmonic optical antenna must exhibit non-toxicity, plasmon resonance in the NIR regime, high local field enhancement, and mobility under physiological conditions. Therefore, the material, size, and structure of the nanoplasmonic optical antenna are designed to simultaneously achieve the aforementioned features. Gold is selected since it is widely accepted as a biocompatible material. The nano-scale size and
Intracellular nanoplasmonic gene switches
Nanoplasmonic gene switches enable temporal and spatial regulation of intracellular genetic activity. Using remote-controlled NIR light as a trigger to release free oligonucleotides and ‘activate’ their functionality, endogenous intracellular genes can be silenced on demand. In addition to the inhibitory effects, exogenous foreign genes can also be introduced and expressed on demand.
Because of their large surface-to-volume ratio, nanoplasmonic gene switches are ideal carriers of
Intracellular PRET biosensors
In addition to on-demand gene regulation, nanoplasmonic optical antennae can also serve as label-free biosensors to significantly enhance spectral information for PRET. Plasmon resonance energy can be transferred from nanoplasmonic optical antennae to biomolecules in proximity. When the plasmon resonance spectrum of an antenna is intentionally matched to the absorption spectrum of the biomolecules, energy transfer by PRET [5••, 6••, 7••] results in wavelength-specific quenching in the Rayleigh
Nanoplasmonic molecular rulers
Biosensors functioning as nanoplasmonic molecular rulers enable label-free measurement of DNA length, real-time kinetic studies of nuclease activity, and real-time detection of specific binding activities between proteins and DNA. A nanoplasmonic molecular ruler utilizes a single gold nanoparticle with tethered double-stranded DNA containing cleavage sites for nucleases. DNA digestion by nucleases resulted in changes in the dielectric constant of the medium locally surrounding the gold
Integrated photoacoustic–photothermal contrast agents
Photoacoustic imaging is a non-invasive technique to image the distribution of optical absorption in tissues. As one of the promising methods for in vivo medical imaging, it is based on the optical absorption of photons. The release of localized heat and the local thermal expansion produces pressure transients. A photoacoustic pulse provides the information of location, absorption, and dimension of the source area. The integration of photoacoustic and photothermal imaging provides optical,
Conclusions
Here, the creative designs of nanoplasmonic optical antennae for quantitative biology and nanomedicine have been discussed. Functioning as nanoplasmonic gene switches, nanoplasmonic optical antennae enable on-demand and precise intracellular regulation of genetic activity. Functioning as label-free biosensors, nanoplasmonic optical antennae enable PRET-based and SERS-based biosensing and molecular imaging of living cells as well as in vitro molecular detection. Nanoplasmonic molecular rulers
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
The authors thank all current and previous BioPOETS for their invaluable scientific contribution to projects discussed in this review. The authors acknowledge the National Institutes of Health (NIH) Nanomedicine Development Center for the Optical Control of Biological Function (PN2 EY018241) for financial support, the Siebel Foundation for graduate support of S.E. Lee (Siebel Scholarship, Class of 2010), and the Center for Nanostructured Materials and Technology (CNMT) of the Korea government.
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