12.1 Challenges Associated with Temperature Stress

Temperature stress is caused by heat or cold and has the potential to interfere with cell structure and function. Examples of temperature stress include hypothermia, hyperthermia, fever, and freezing. In the rest of this chapter, we will explore why most organisms and their cells are adapted to a small range of environmental temperatures, challenges cells face when dealing with temperatures outside of their optimal range, and how cells detect and respond to various temperature stresses. We will specifically cover freezing stress in Chapter 13.

Cellular and Organismal Function Under Optimal Temperature Conditions

Almost all cells have a thermal optimal zone, the temperature range in which the cell can function best. It is within this temperature range that cells can most effectively grow, reproduce, or perform other functions. Different organisms have different thermal optima, depending on their physiology and the environments they are adapted to. For example, icefish (Channichthyidae funnari) are Antarctic fish that live in very cold environments and are well adapted to their thermal optimum of almost 0°C (Figure 12.2A). ^[1]Conversely, Pyrolobus fumarii is a hyperthermophile archaean species found at the deep-sea vents and have an optimal temperature of 106°C (Figure 12.2B).  Some organisms (e.g., mammals and birds) expend considerable energy to maintain a constant and warm body temperature so their cells are always at the thermal optimum. However, most organisms do not generate substantial internal heat to heat their cells, and they must be able to function at the temperature of the environment in which they live.

Because thermal optima vary among species, the temperatures that cause stress also vary among species. For example, what might be comfortable for humans (e.g., room temperature of 20°C) would be a high temperature stress for the ice fish and a low temperature stress for the thermophilic Archaean described above. Temperatures slightly above or below an organism’s optimal zone are still manageable but can cause mild temperature stress on the cell. Temperatures that are far above or below this thermal optimum zone will cause extreme temperature stress. During extreme temperature stress, there can be massive damage to cells, and sometimes even cell death. Later in this chapter, we will explore specific challenges that cells face when dealing with temperature stress, as well as different ways of detecting and responding to these stresses.

Challenges Associated with Temperature Stress

Changes in temperature are challenging to cells because temperature has such a strong impact on the structure of proteins and lipids, both of which are very important for cell structure and function. A change in temperature above or below the thermal optimum can therefore have a large impact on cells simply due to the physical impact of temperature on these macromolecules, which we summarize below.

The Impact of Temperature on Proteins

As described in Chapter 3.4, proteins are an essential macromolecule and can be found in all cells. Some of the most important tasks completed by proteins inside cells include: structural support, catalysis of chemical reactions, and cellular maintenance. Additionally, proteins play a significant role within multicellular organisms by facilitating cell-to-cell connections and communication. Each protein has an optimal temperature at which their activity is maximized (Figure 12.3). Protein structure is stabilized by many weak bonds such as hydrogen bonds, ionic bonds, and van der Waals interactions, all of which are impacted by temperature.

When an organism is exposed to mild changes in temperature, there is an increase or decrease in protein flexibility that often inhibits function. Mild increases in temperature increase the flexibility of proteins by loosening some of the weak interactions that stabilize protein structure, which can make the protein too flexible to function properly. Mild decreases in temperature will increase the strength of those weak interactions, decreasing protein flexibility, which can make the protein too inflexible to function properly. Protein function will return to normal if the temperature is restored to the optimum temperature, because the influence of mild changes in temperature is not intense enough to permanently denature (unfold) the proteins.

Extreme high or low temperatures can denature proteins, causing the protein to become unfolded. Once a protein is unfolded, it is no longer functional. Denatured proteins are susceptible to protein aggregation, where unfolded proteins are attracted to one another and create potentially toxic accumulations of protein within the cell (Figure 12.4). The lack of protein activity at extremely high temperatures (activity = 0 in Figure 12.3) is usually caused by denaturation. Extreme low temperatures can also cause denaturation (not shown in Figure 12.3).

Consequences of Low to Non-Functioning Proteins

As a result of mild to extreme temperature changes, proteins experience moderate to severe conformational changes that inhibit or arrest protein function. The inhibition or cease of protein functioning has negative consequences for a variety of cellular processes including: metabolic processes (including ATP production), transmembrane transport activity, ion and water balance, and cytoskeletal integrity.

Metabolic processes are impacted by temperature stress because most enzymes are proteins. Enzymes play an essential role in the catalysis of chemical reactions within all metabolic pathways including those that generate ATP. Due to the temperature-sensitivity of proteins, mild changes in temperature usually decrease but do not completely inhibit enzyme function. Low temperatures slow down enzyme function, as well as chemical reaction rates. Although increasing temperatures can increase reaction rates, if the temperature gets high enough to impair enzyme function, we will start to see reactions rates decrease. Both extreme low and high temperatures can denature enzymes, preventing them from catalyzing reactions (Figure 12.5). The consequences for the rest of the organism include greatly reduced ATP production, and the inability of metabolic processes to occur. As metabolic processes are essential for energy production and survival, this is an extremely significant challenge posed by temperature stress.

Transmembrane transport is impacted by temperature stress because lots of transmembrane transport is facilitated by proteins. Like enzymes, transmembrane transport proteins (e.g., ion pumps) are temperature sensitive. Under mild low or high temperature stress, transport proteins exhibit decreased functionality. Ion pumps (e.g., Na⁺/K⁺ ATPase; see Chapter 5.4) also require ATP to function, so limited ATP availability during mild temperature stress can cause reduced ion transport in and out of the cells, resulting changes to the ion and water balance of the cell. As temperature changes become more extreme, this can result in the denaturation of the transmembrane transport proteins. The ability for cells to regulate solute movement becomes non-existent. Solutes may rapidly enter the cell, followed by an influx of water, leading to cell swelling and subsequent lysis. Alternatively, solutes may rapidly leave the cell to enter the extracellular matrix, followed by water, resulting in cell dehydration. In either case, the cells lose their homeostatic balance and experience an extreme loss of function or may even become non-functional. An example of this is at low temperatures, a loss of ion and water balance results in a chill coma (loss of locomotion caused by low temperature) in ectothermic animals, where their muscles and neurons do not work.

As discussed in Chapter 4.5, cytoskeletal filaments are also composed of proteins. In particular, each microfilament, intermediate filament, and microtubule consists of multiple subunit proteins that are held together via weak interactions. An increase or decrease in temperature can disrupt these weak interactions, causing the cytoskeletal protein subunits to dissociate from each other, causing depolymerization of the cytoskeletal filaments. In addition, the stability of microfilament and microtubule structure depends on a constant supply of ATP or its equivalent. If ATP availability is low due to the impact of temperature on metabolism, it becomes even more challenging for cells to maintain their cytoskeletal structure. If cytoskeletal structure is disrupted, this can negatively impact all processes associated with the cytoskeleton, including the support of cell structure, movement of cells, and movement of substances within cells.

The Impact of Temperature on Membranes

Cellular membranes (see Chapter 5.1) are influenced by temperature and, much like proteins, function optimally within a specific temperature range. For the membrane to function properly, it must be in the liquid crystalline phase, a fluid state in which phospholipids and their fatty acid tails can move, but still make up a stable boundary for the cell. Changes in temperature alter (increase or decrease) membrane fluidity, which can have grave consequences for the cell.

Mild changes in temperature cause an increase or decrease in membrane fluidity, but the membrane remains within the liquid crystalline state. As temperatures increase, the fatty acid tails of the phospholipid bilayer exhibit more movement and increase the fluidity of the membrane. Cold temperatures increase the rigidity of the fatty acid tails of the phospholipid bilayer, decreasing the fluidity of the membrane. Small changes in fluidity of the liquid crystalline phase can impair various membrane processes such as transport of solutes across the membrane, cellular signalling such as cell to cell communication, as well as processes that require changes in membrane shape such as endo- and exocytosis.

Extreme changes in temperature pose a significant challenge by causing a state transition of the membrane – to gel phase or totally fluid phase. Every lipid bilayer has a specific transition temperature where it goes from fluid (liquid crystalline) to solid. To maintain the liquid crystalline state, the temperature must remain above the transition temperature. If the temperature drops below the transition temperature, the membrane transitions into a more solidified state (Figure 12.6), and any membrane functions that depend on optimal membrane fluidity will be slowed considerably. These changes to membrane fluidity caused by prolonged temperature changes may result in permanent membrane damage. Extreme high temperatures can cause membranes to be too fluid (Figure 12.6), which can compromise membrane integrity. Breaks in the membrane caused by phase changes can result in cell death.