Express assessment of neurotoxicity of particles of planetary and interstellar dust

Express assessment of neurotoxicity of particles of planetary and interstellar dust

Express on-board assessment of the neurotoxicity of planetary and interstellar dust particles will be required to predict their potential threat to human health during long-term space missions. The toxicity of particles depends not only on their size, but also on their composition, shape, charge, surface properties and ability to absorb toxic substances from the environment. It is difficult to make a predictive model for particle toxicity without experimental measurements because of the huge diversity of particle characteristics and their unknown effects. Furthermore, even a small variation of particle size, charge, shape, and functional group exposure can unpredictably alter their properties. Measurements of these characteristics require complex and sophisticated equipment, complicated techniques and the existence of well-functioning biological models, for example cell culture, tissue preparations, and animals, which may not be readily amenable to direct testing in space flight.

During inhalation, nanoparticles can accumulate in the nasal regions, where they are then transported along sensory axons of the olfactory nerve directly to the central nervous system. The plasma membrane of the cells is involved in cellular functioning, and in particular, the plasma membrane of nerve cells, is directly involved in nerve signal transmission and simultaneously performs a classical barrier function, which is interrupted during contact with dust particles. The complex characteristics of the particles determine their capacity to affect integrity of the cellular plasma membrane. An approach for the rapid assessment of potential neurotoxicity of micro-sized and nano-sized dust particles based on experimental results with other neurotoxic particles was proposed. Capacity of particles to affect membrane potential, integrity of nerve terminals and consequently key synaptic transmission characteristics can be assessed by monitoring artificial membrane conductivity using a planar lipid bilayer technique. This is a well-known technique for investigation of ion-conducting properties of pore-forming molecules and proteins, ion channels, and transporters. Single, stable lipid bilayers between two compartments filled with saline were formed by Mueller et al. (Nature, 1962). Planar lipid bilayers are usually composed of phosphatidylcholine and cholesterol, however other lipid and protein components can be also included. Bilayer membranes are usually painted across a round aperture with a small mm-sized diameter in a thin wall of a Teflon cup held within a glass chamber. A high resolution amplifier and computer are used for voltage-clamp recordings of transmembrane current. Monitoring the membrane activity of micro-sized and nano-sized dust particles during long-term space flight could potentially be implemented using an adapted planar lipid bilayer technique through registration of artificial membrane conductivity in the presence of particles. Ion conductance of the planar lipid bilayer might correlate with the capacity of the acquired planetary dust particles, once added to the operation cuvette, to affect the membrane integrity.

However, extensive validation is required to have appropriate assessment algorithms and the parameter relations for different types of particles. The results from planar lipid bilayer measurements might supplement data obtained by other techniques. To support experimentation in space, the planar lipid bilayer technique would need to be adapted to be portable, automated, vibration-resistant, and suitable to perform measurements in a simple manner, thereby making the monitoring process manageable for those on board.

If implemented, this approach might also be applicable to environmental monitoring for the assessment of toxicity of air pollution particulate matter on Earth and in nanotechnology for estimation of biosafety of engineered nanoparticles. Ultimately, it is hoped that the associated acquired knowledge could be of value for the prediction and prevention of harmful human health effects of particle inhalation. Under space flight conditions, toxicity assessments of particulate matter could be rapidly and reproducibly performed using a planar lipid bilayer technique, which does not require biological material.


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