Low Density Lipoproteins as Circulating Fast Temperature Sensors

Background: The potential physiological significance of the nanophase transition of neutral lipids in the core of low density lipoprotein (LDL) particles is dependent on whether the rate is fast enough to integrate small (62uC) temperature changes in the blood circulation. Methodology/Principal Findings: Using sub-second, time-resolved small-angle X-ray scattering technology with synchrotron radiation, we have monitored the dynamics of structural changes within LDL, which were triggered by temperature-jumps and-drops, respectively. Our findings reveal that the melting transition is complete within less than 10 milliseconds. The freezing transition proceeds slowly with a half-time of approximately two seconds. Thus, the time period over which LDL particles reside in cooler regions of the body readily facilitates structural reorientation of the apolar core lipids. Conclusions/Significance: Low density lipoproteins, the biological nanoparticles responsible for the transport of cholesterol in blood, are shown to act as intrinsic nano-thermometers, which can follow the periodic temperature changes during blood circulation. Our results demonstrate that the lipid core in LDL changes from a liquid crystalline to an oily state within fractions of seconds. This may, through the coupling to the protein structure of LDL, have important repercussions o

Sketch of the experimental setup.

<p>The experimental arrangement for time-resolved X-ray measurements at the Austrian SAXS–beamline at the ELETTRA synchrotron light source is shown. For T-jump experiments, an erbium laser beam (IR), wavelength λ = 1.5 µm, was directed via a prism onto the sample capillary which was thermostated with a Peltier unit. Laser pulse energy was 2 J within 2 ms resulting in an average T-jump amplitude of 10–12°C. The exposure time was 10 ms per frame. For T-drop experiments, the empty X-ray capillary was pre-cooled in a stream of nitrogen adjusted to −20°C. LDL samples, preheated to approx.10°C above the melting transition, were injected by a motor-driven syringe. A drop in temperature of about 20°C could be induced in about 3–4 s. The exposure time was 250 ms per frame.</p

Time-resolved nanophase transition in LDL.

<p>The rise in the integrated intensity of the 1st side-maximum upon laser jump is shown as a function of time (A). The time slicing was 10 ms per image. The time point of laser flash is set to zero seconds. The error function of statistical variation displays a maximum inaccuracy in time of about 5 ms. Thus, the offset in transition is much shorter than the sampling time of 10 ms and the 2 ms of laser flash. The integrated intensities of the 1st side-maximum obtained by static measurements within a temperature range of 0°C and 50°C with a step width of 5°C (B, left panel) are correlated to the time-course of integrated intensities of the 1st side-maximum obtained by dynamic measurements (B, right panel). For static measurements, a measuring time of 30 s and an equilibration time of 10 minutes at each temperature was chosen. For dynamic measurements, the measuring time per frame was 250 ms. A half-time of 2 seconds, corresponding to a temperature drop of about 10°C, could be achieved to pass through the transition temperature. The decline in integrated intensity strictly followed the drop in temperature. Tm for the LDL sample shown was about 22°C, as determined by microcalorimetry.</p