Tag Archives: dynamics

Corona-induced transition from molecular to particle motion in biological media

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Light signatures generated by particles in a nanoscopeIn last month’s post [see ‘Nanoparticle motion through heterogeneous hydrogels’ on November 6th, 2024], I described our recent work on tracking nanoparticles through a model of the vitreous humour and mentioned it was the first of two articles published in the Nature journal, Scientific Reports.  In the second article, we explored the use of caustics in an optical microscope [see ‘Seeing the invisible’ on October 29th, 2014] to track nanoparticles in biofluids.  Nanoparticles are below the resolution of an optical microscope because they are substantially smaller than the wavelength of visible light; hence, they are usually tracked using fluorescent markers or tags attached chemically to the nanoparticles.  These tags can influence both the motion of the particles and biological activity so caustics provide a label-free technique that allows particles to be tracked in real-time using a standard optical microscope.  In most of our previous research, we have tracked nanoparticles in transparent fluids such as water, glycerol-water mixtures, or the hydrogels described in last month’s post.  In our latest work, we have tracked small nanoparticles with diameters from 10 to 100 nm in common cell culture media with different concentrations of serum proteins.  These fluids are a ‘soup’ of complex protein molecules that interact with one another and the gold nanoparticles being tracked.  We found that the presence of proteins caused a reduction in the rate of diffusion for both positively- and negatively-charged particles and we concluded that the proteins form a corona around each nanoparticle effectively enlarging its diameter.  For larger nanoparticles, and those positively-charged, the enlargement appears to cause a transition from molecular motion, in which particle diameter is unimportant, to particle motion where larger particles diffuse more slowly.  We first explored this transition from fractional to classical Stokes-Einstein behaviour in simple fluids in 2017 [‘Slow moving nanoparticles‘ on December 13th 2017] and it seems likely to be complicated in these complex fluids.  Hence, understanding protein dynamics as well nanoparticle dynamics will be essential to the development of nanotechnologies applicable in biological environments.  So, we have lots more work to do!

Sources:

Schleyer G, Patterson EA, Curran JM. Label free tracking to quantify nanoparticle diffusion through biological media. Scientific Reports. 2024 Aug 13;14(1):18822.

Coglitore D, Edwardson SP, Macko P, Patterson EA, Whelan MP, Transition from fractional to classical Stokes-Einstein behaviour in simple fluids, Royal Society Open Science, 4:170507, 2017.

Happy New Year!

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Decorative photograph of sculpture of a skeletal person leading a skeletal dinosaurThis year I have written about 20,000 words in 52 posts (including this one); and, since this is the last post of the year, I thought I would take a brief look back at what has preoccupied me in 2021.  Perhaps, not surprisingly the impact of the coronavirus on our lifestyle has featured regularly – almost every week for a month between mid-March and mid-April when we were in lockdown in the UK.  However, the other topics that I have written about frequently are my research on the dynamics of nanoparticles and, in the last six months, on dealing with uncertainty in digital engineering and decision making.  I have also returned several times to innovation processes and transitioning lab-based research into industry.  While following the COP26 in early November, I wrote a series of three posts focussed on energy consumption and the paradigm shifts required to slow down climate change.  There are some connections between these topics: viruses are nanoparticles whose transport and dynamics we do not fully understand; and, digital engineering tools are being used to explore zero-carbon approaches to, for example, energy generation and air transport.  The level of complexity, innovation and urgency associated with developing solutions to these challenges mean that there are always some unknowns and uncertainty when making associated decisions.

The links below are grouped by the topics mentioned above.  I expect there will be more on all of these topics in 2022; however, the topic of next week’s post is unknown because I have not written any posts in advance.  I hope that the uncertainty about the topic of the next post will keep you reading in 2022! 

Coronavirus pandemic: ‘Distancing ourselves from each other‘ on January 13th, 2021; ‘On the impact of writing on well-being‘ on March 3rd, 2021; ‘Collegiality as a defence against pandemic burnout‘ on March 24th, 2021; ‘It’s tiring looking at yourself‘ on March 31st, 2021; ‘Switching off and walking in circles‘ on April 7th, 2021; ‘An upside to lockdown‘ on April 14th, 2021; ‘A brief respite in a long campaign to overcome coronavirus‘ on June 23rd, 2021; and ‘It is hard to remain positive‘ November 3rd 2021.

Energy and climate change: ‘When you invent the ship, you invent the shipwreck‘ on August 25th, 2021; ‘It is hard to remain positive‘ November 3rd 2021; ‘Where we are and what we have‘ on November 24th, 2021; ‘Disruptive change required to avoid existential threats‘ on December 1st, 2021; and ‘Bringing an end to thermodynamic whoopee‘ on December 8th, 2021.

Innovation processes: ‘Slowly crossing the valley of death‘ on January 27th, 2021; ‘Out of the valley of death into a hype cycle?‘ on February 24th, 2021; ‘Innovative design too far ahead of the market?‘ on May 5th, 2021 and ‘Jigsaw puzzling without a picture‘ on October 27th, 2021.

Nanoparticles: ‘Going against the flow‘ on February 3rd, 2021; ‘Seeing things with nanoparticles‘ on March 10th, 2021; and ‘Nano biomechanical engineering of agent delivery to cells‘ on December 15th, 2021.

Uncertainty: ‘Certainty is unattainable and near-certainty is unaffordable‘ on May 12th, 2021; ‘Neat earth objects make tomorrow a little less than certain‘ on May 26th, 2021; ‘Negative capability and optimal ambiguity‘ on July 7th, 2021; ‘Deep uncertainty and meta ignorance‘ on July 21st, 2021; ‘Somethings will always be unknown‘ on August 18th, 2021; ‘Jigsaw puzzling without a picture‘ on October 27th, 2021; and, ‘Do you know RIO?‘ on November 17th, 2021.

Nano biomechanical engineering of agent delivery to cells

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figure 1 from [1] with text explanationWhile many of us are being jabbed in the arm to deliver an agent that stimulates our immune system to recognize the coronavirus SARS-CoV-2 as a threat and destroy it, my research group has been working, in collaboration with colleagues at the European Commission Joint Research Centre, on the dynamics of nanoparticles [1] [see ‘Size matters‘ on October 23rd, 2019] which could be used as carriers for the targeted delivery of therapeutic, diagnostic and imaging agents in the human body [2].  The use of nanoparticles to mechanically stimulate stem cells to activate signalling pathways and modulate their differentiation also has some potential [3]. In studies of the efficacy of nanoparticles in these biomedical applications, the concentration of nanoparticles interacting with the cell is a primary factor influencing both the positive and negative effects.  Such studies often involve exposing a monolayer of cultured cells adhered to the bottom of container to a dose of nanoparticles and monitoring the response over a period of time.  Often, the nominal concentration of the nanoparticles in biological medium supporting the cells is reported and used as the basis for determining the dose-response relationships.  However, we have shown that this approach is inaccurate and leads to misleading results because the nanoparticles in solution are subject to sedimentation due to gravity, Brownian motion [see ‘Slow moving nanoparticles‘ on December 13th, 2017] and inter-particle forces [see ‘ Going against the flow‘ on February 3rd, 2021] which affect their transport within the medium [see graphic] and the resultant concentration adjacent to the monolayer of cells.  Our experimental results using the optical method of caustics [see ‘Holes in fluids‘ on October 22nd, 2014] have shown that nanoparticle size, colloidal stability and solution temperature influence the distribution of nanoparticles in solution.  For particles larger than 60 nm in diameter (about one thousandth of the diameter of a human hair) the nominal dose differs significantly from the dose experienced by the cells.  We have developed and tested a theoretical model that accurately describes the settling dynamics and concentration profile of nanoparticles in solution which can be used to design in vitro experiments and compute dose-response relationships.

References

[1] Giorgi F, Macko P, Curran JM, Whelan M, Worth A & Patterson EA. 2021 Settling dynamics of nanoparticles in simple and biological media. Royal Society Open Science, 8:210068.

[2] Daraee H, Eatemadi A, Abbasi E, Aval SF, Kouhi M, & Akbarzadeh A. 2016 Application of gold nanoparticles in biomedical and drug delivery. Artif. Cells Nanomed. Biotechnol. 44, 410–422. (doi:10.3109/21691401.2014.955107)

[3] Wei M, Li S, & Le W. 2017 Nanomaterials modulate stem cell differentiation: biological
interaction and underlying mechanisms. J. Nanobiotechnol. 15, 75. (doi:10.1186/s12951-
017-0310-5)

From strain measurements to assessing El Niño events

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Figure 11 from RSOS 201086One of the exciting aspects of leading a university research group is that you can never be quite sure where the research is going next.  We published a nice example of this unpredictability last week in Royal Society Open Science in a paper called ‘Transformation of measurement uncertainties into low-dimensional feature space‘ [1].  While the title is an accurate description of the contents, it does not give much away and certainly does not reveal that we proposed a new method for assessing the occurrence of El Niño events.  For some time we have been working with massive datasets of measurements from arrays of sensors and representing them by fitting polynomials in a process known as image decomposition [see ‘Recognising strain‘ on October 28th, 2015]. The relatively small number of coefficients from these polynomials can be collated into a feature vector which facilitates comparison with other datasets [see for example, ‘Out of the valley of death into a hype cycle‘ on February 24th, 2021].  Our recent paper provides a solution to the issue of representing the measurement uncertainty in the same space as the feature vector which is roughly what we set out to do.  We demonstrated our new method for representing the measurement uncertainty by calibrating and validating a computational model of a simple beam in bending using data from an earlier study in a EU-funded project called VANESSA [2] — so no surprises there.  However, then my co-author and PhD student, Antonis Alexiadis went looking for other interesting datasets with which to demonstrate the new method.  He found a set of spatially-varying uncertainties associated with a metamodel of soil moisture in a river basin in China [3] and global oceanographic temperature fields collected monthly over 11 years from 2002 to 2012 [4].  We used the latter set of data to develop a new technique for assessing the occurrence of El-Niño events in the Pacific Ocean.  Our technique is based on global ocean dynamics rather than on the small region in the Pacific Ocean which is usually used and has the added advantages of providing a confidence level on the assessment as well as enabling straightforward comparisons of predictions and measurements.  The comparison of predictions and measurements is a recurring theme in our current research but I did not expect it to lead into ocean dynamics.

Image is Figure 11 from [1] showing convex hulls fitted to the cloud of points representing the uncertainty intervals for the ocean temperature measurements for each month in 2002 using only the three most significant principal components . The lack of overlap between hulls can be interpreted as implying a significant difference in the temperature between months.

References:

[1] Alexiadis, A. and Ferson, S. and  Patterson, E.A., , 2021. Transformation of measurement uncertainties into low-dimensional feature vector space. Royal Society Open Science, 8(3): 201086.

[2] Lampeas G, Pasialis V, Lin X, Patterson EA. 2015.  On the validation of solid mechanics models using optical measurements and data decomposition. Simulation Modelling Practice and Theory 52, 92-107.

[3] Kang J, Jin R, Li X, Zhang Y. 2017, Block Kriging with measurement errors: a case study of the spatial prediction of soil moisture in the middle reaches of Heihe River Basin. IEEE Geoscience and Remote Sensing Letters, 14, 87-91.

[4] Gaillard F, Reynaud T, Thierry V, Kolodziejczyk N, von Schuckmann K. 2016. In situ-based reanalysis of the global ocean temperature and salinity with ISAS: variability of the heat content and steric height. J. Climate. 29, 1305-1323.