Water Dynamics in Cancer Cells: Lessons from Quasielastic Neutron Scattering

Abstract

The severity of the cancer statistics around the globe and the complexity involving the behavior of cancer cells inevitably calls for contributions from multidisciplinary areas of research. As such, materials science became a powerful asset to support biological research in comprehending the macro and microscopic behavior of cancer cells and untangling factors that may contribute to their progression or remission. The contributions of cellular water dynamics in this process have always been debated and, in recent years, experimental works performed with Quasielastic neutron scattering (QENS) brought new perspectives to these discussions. In this review, we address these works and highlight the value of QENS in comprehending the role played by water molecules in tumor cells and their response to external agents, particularly chemotherapy drugs. In addition, this paper provides an overview of QENS intended for scientists with different backgrounds and comments on the possibilities to be explored with the next-generation spectrometers under construction.

Keywords: cancer cells; quasielastic neutron scattering; water dynamics.

Figure 1

(a) Typical scattering triangle showing incoming neutrons with incident energy E_i, wavelength λ_i, and wave vector $\overrightarrow{k_i}$ interacting with the sample and assuming final energy E_f, wavelength λ_f, and wave vector $\overrightarrow{k_f}$. The momentum transfer $\overrightarrow{Q}$ is defined as the change in wave vector ($\overrightarrow{Q}$= $\overrightarrow{k_i}$− $\overrightarrow{k_f}$); (b) summary of the main features of the QENS technique. These are explained in detail in the text.

Figure 2

Graphical representation of a single particle scattering. The incoming neutron waves are scattered by a particle i at different times, 0 and t, and positions, $\overrightarrow{r_i\left(0\right)}$ and $\overrightarrow{r_i\left(t\right)}.$ The scattered waves interfere with each other before detection. The scattering triangle is also represented in the figure.

Figure 3

Schematics of the relationship between I_incoh(Q, t) and S_incoh(Q, $\omega$). In (a), curve a-I shows the expected behavior of I_incoh(Q, t) for a static particle where no exchange of energy occurs between the incoming neutrons and the sample. As shown in a-II, after a time-Fourier transformation of I_incoh(Q, t), one obtains a δ-function-shaped S_incoh(Q, $\omega$), which broadens when convoluted with the experimental resolution (see a-III). In (b), the particles under analysis perform motions upon, for example, heating and I_incoh(Q, t) gradually decays (b-II) and S_incoh(Q, $\omega$) becomes broader (b-II). In (c), an unconstrained diffusive motion is depicted, which leads to a gradual decay of I_incoh(Q,t) over Q (c-I) reaching the limit of I_incoh(Q, $\infty$) = 0, and S_incoh(Q, ω) broadens as a function of Q (c-II). In (d), the motions of particles within a constrained geometry are depicted and I_incoh(Q, t) plateaus at a finite value at $t\to \infty$.

Figure 4

Illustration of the complex chemical environment within living cells and the different water populations. The green/pink molecules depict the bulk-like populations, which are subjected to weak interactions with the biological interfaces and are more abundant in cellular media (they are semi-transparent in the figure for presentation purposes). The red/blue molecules depict the confined-like populations, which are subjected to closer interactions with the biological interfaces and present features of confined dynamics that are not comparable with bulk water.

Figure 5

Schematics of the different outcomes obtained in QENS experiments with cancer cells.

Figure 6

Variation of the full widths at half-maximum (FWHM) with Q² for untreated and cisplatin-treated (8 and 20 mM) MDA-MB-231 cells in deuterated saline medium (washed), at 298 k: (a) Lorentzian functions representing the translational motions of intracellular water—cytoplasmic and hydration water; (b) Lorentzian function representing the internal localized motions within the cell. Reprinted with permission from ref. [53]. Copyright 2017 The Royal Society of Chemistry.

Figure 7

Dynamic susceptibilities obtained from QENS data for not-treated breast cancer cells (MCF-7), NTC (a), and breast cancer cells treated with 15nM of paclitaxel for 24 h, TC (b), reprinted from [16] available via the Creative Commons Attribution 4.0 International License (CCBY4.0, https://creativecommons.org/licenses/by/4.0/, 29 March 2022).