MST - Microscale Thermophoresis

Please acknowledge the SIP core facility ( RRID: SCR_018986) in publications, on posters, or in talks if you use any instruments in the SIP core facility. Please include SIP's RRID (RRID: SCR_018986) and the grant numbers for instruments funded through instrumentation grants in your acknowledgements. This is a requirement from the funding agencies and is crucial for future funding. Find example text on theÌýAcknowledgement PageÌýor the individual instrument pages.

MST in in Biochemistry, Biophysics and Structural Biology

Microscale Thermophoresis (MST) is a biophysical technique used to study molecular interactions by detecting changes in the movement of biomolecules and complexes along a temperature gradient.Ìý

When subjected to a localised temperature increase, molecules experience a shift in their mobility, a process known as thermophoresis. The extent of this movement is dependent on the size, charge, and hydration shell of the molecule or complex. During most binding events, one or several of these properties will change, making MST a powerful technique for the quantitative analysis of binding reactions.Ìý

By labelling one of the interacting partners with a fluorescent dye, MST monitors changes in fluorescence intensity as the labelled molecule moves in response to a small temperature gradient. The highly localised temperature gradient is induced with an infrared laser (1480 nm wavelength) focused onto a small spot on the sample capillary where the fluorescence intensity is measured. When binding occurs, the thermophoretic properties of the labelled molecule change, enabling the detection and quantification of molecular interactions based on changes in fluorescence intensity due to thermophoretic movement. By analysing these shifts over a series of different concentrations, MST provides detailed information on binding affinities.

MST can measure dissociation constants (Kd) from the nanomolar (nM) to millimolar (mM) range. It is applicable to various interactions, including protein-protein, protein-ligand, DNA/RNA-ligand, DNA/RNA-protein, protein-lipid, peptide-lipid, small molecule binding, and membrane proteins in liposomes, nanodiscs, or detergent solutions.

MST traces and data fit for 16 point titration reaction

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Key highlights of MST in Biology, Biochemistry, and Biophysics

  • Dissociation constants (Kd) ranging from nM to mM.
  • Measurements under equilibrium conditions in solution.
  • Very few buffer restrictions; measurements possible in complex buffers or even in lysates under near-physiological conditions.
  • Applicable to various interactions: protein-protein, protein-ligand, DNA/RNA-ligand, DNA/RNA-protein, protein-lipid, peptide-lipid, small molecule binding, and membrane proteins in liposomes, nanodiscs, or detergent solutions.
  • No immobilisation and no size limitations.
  • Flexible labelling options, with the label positioned far from the interaction site to minimise interference with binding.
  • Low sample consumption.
  • Determine stoichiometry and number of binding sites.
  • Investigate oligomerisation and aggregates.
MST

Instrument and Accesories

Our MST instrument is a Nano-BLUE/RED Monolith NT.115 from NanoTemper Technologies.Ìý

It has two LED-filter combinations:

  • blue (excitation 450–480 nm, emission 515–570 nm) Ìý
  • red (excitation 600–645 nm, emission 670–730 nm)

Essential Information for Using SIP's MST

Why?

Acknowledgements are essential for ensuring the continued success of the Shared Instruments Pool (SIP). They enable us to secure the necessary funding to sustain and expand the SIP, ensuring that our instruments are in optimal working condition and that the methods we offer are at the forefront of biochemical and biophysical research.

Please include SIP's RRID number (RRID: SCR_018986) in your acknowledgements. This allows funding organisations and potential grant reviewers to easily locate publications supported by SIP, helping to evaluate the impact of SIP on our research community.

If facility staff have provided substantial assistance, please consider acknowledging them. If they contributed significantly to the intellectual aspects or conducted important experiments, co-authorship may also be appropriate.

Example text:

We thank the Shared Instruments Pool (RRID: SCR_018986),Department of Biochemistry, University of Colorado Boulder for the use of the MST (BLUE/RED Monolith NT.115, NanoTemper Technologies) . The CD was funded by NIH S10OD021603. We also thank [Name and title of the facility member providing significant help] for their invaluable assistance with data collection and evaluation.

Please contact Dr Erbse to obtain detailed protocols and arrange an initial project consultation and personalised training sessions. Protocols are available as PDF files on the instrument computers, with printed copies stored alongside the instruments.

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Interested users can contact Dr Erbse to discuss planned experiments and arrange training sessions. These sessions will involve the use of actual user samples alongside standards, enabling users to collect preliminary data during the training and receive help from core staff right away if troubleshooting or optimisation is needed. Users are welcome to request additional training or support sessions at any time. We are always happy to provide a refresher if it has been a while.

After your training is completed, you will be invited to join the MST Google calendar.

Sign Up Rules:Ìý
Up to Friday the week before the planned experiment users can sign up for a maximum of 2 days. In the week of the experiment users can sign up for additional time if available.

  • Initial consultation is free. SIP staff are happy to assist with a short pilot experiment if it can be accommodated within SIP's resources.
  • Regular user groups are expected to buy into SIP with a monthly flat fee according to their SIP usage level. For detailed information, please contact Dr Annette Erbse.
  • Users are required to provide all consumables specific to their experiments. This includes capillaries and labelling kits. ÌýA limited amount of capillaries for pilot experiments are available.
  • Costs for necessary repairs, services, or replacement parts due to normal wear and tear will be shared among all user groups, based on the time used over the past two years. Please note that assuming the instrument is handled properly, such repairs or replacements are infrequent, and costs may arise after a user’s period of use has ended.
  • Users are responsible for covering the costs of repairs or replacement parts needed due to damage caused by carelessness or neglect.

The MST is located on the basement of JSCBB in the C-Wing, room C1B60, on East Campus. Proxcard access is required at all times.