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Time Domain NMR in the Assessment of Nanofluidity in Biological Systems

“.. benchtop time-domain NMR is capable of resolving two to four T2 domains in biologically relevant long chain fatty acids”

Nuclear magnetic resonance (NMR) provides the basis for a wide range of powerful analytical methodologies. Although each is distinct, they are all based on the principle that exposure to a magnetic field, causes nuclei to be elevated to a higher energy level, and this energy transfer is reversed on removal of the magnetic field. The diverse techniques can be broadly categorised as NMR spectroscopy, NMR imaging or time domain NMR (also known as NMR relaxometry).

NMR spectroscopy, which measures the radiofrequency of the energy released when the excited nuclei return to their base energy level, has been dominating NMR technology for many years. An explosion of innovation and technological advances in NMR spectroscopy has revolutionised biological research by enabling the characterisation of increasingly complex molecules. The technique gives a high level of detail and spatial resolution and has been pivotal in the elucidation of protein structure and function.

More recently, there has been increasing interest in the less powerful time domain NMR that is not limited by the expense and size of the more sophisticated NMR spectroscopy. Time domain NMR does not require the high-field superconducting magnets needed to achieve chemical shift resolution in NMR spectroscopy and imaging. It can be conducted with much smaller, less expensive low-field permanent magnets. Consequently, time domain NMR can be achieved with compact bench-top instrumentation, which not only makes it more widely accessible but also allows NMR technology to be portable.

Time domain NMR measures the time required for nuclei to return to equilibrium after excitation. Although it sacrifices the power of atomic or spatial resolution, it is a reliable, convenient, rapid analytical methodology. It shows high reproducibility without the need for sample preparation and is non-destructive. Furthermore, it can be used on a greater range of sample types than NMR spectroscopy. Time domain NMR instruments can accommodate semi-solid or liquid crystalline samples and heterogeneous samples.

The simpler technique can adequately address numerous analytical tasks. Indeed, time domain NMR is being used in a wide variety of settings beyond the specialized NMR laboratory or imaging centre and is being employed in an ever-increasing range of applications. Current uses of time domain NMR include quality testing in the petrochemical and food industries and diagnostic blood tests, eg, for insulin resistance.

Time domain NMR has recently been used in the study of hydrocarbon chain fluidity1 that is known to be a key determinant of cell surface receptor function in biological membranes2.

Researchers measured the fluidity of a series of single-phase fatty acid oils using time domain NMR with a Bruker mq40 minispec time domain benchtop NMR relaxometer with a permanent magnet, and experimentally using a viscometer. The spin−spin relaxation time constants (T2) obtained by time domain NMR correlated with the direct measurements of fluidity. Furthermore, time domain NMR was able to distinguish between the difference domains of the hydrocarbon chain based on differences in hydrocarbon chain structure and composition. T2 values for each domain of the hydrocarbon chain showed positive linear correlations with fluidity.

These data indicate the significant resolving power achievable with time domain NMR using benchtop instrumentation and highlight the potential for time domain NMR to be used to monitor nanofluidity in other biological systems.

References

  1. Robinson MD and Cistola DP. Nanofluidity of Fatty Acid Hydrocarbon Chains As Monitored by Benchtop Time-Domain Nuclear Magnetic Resonance. Biochemistry 2014, 53, 7515−7522.
  2. Nicolson G. The fluid mosaic model of membrane structure: Still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years. Biochim. Biophys. Acta 2014;1838:1451−

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