How large are the volume changes accompanying protein transitions and binding?

We present a simple model to describe volume changes accompanying protein folding and binding events. The model enables one to resolve the changes in volume accompanying conformational transitions of proteins as well as association of proteins with other molecules in terms of the intrinsic, thermal and interaction (hydration) contributions. The thermal contribution to protein volume results from thermally activated mutual vibrational motions of contacting solute and solvent molecules. Our calculations suggest that near zero volume changes accompanying protein folding and binding events reflect compensation between significant changes in the intrinsic, thermal and interaction terms. We have quantitatively estimated these terms as a function of the protein's molecular weight and degree of its unfolding. Results described in this work lay foundation for more reliable and physically justified interpretations of volumetric data on protein folding and binding events. We also discuss potential ways of extending applications of our model to analyzing other macromolecular systems and events, including drug-DNA and protein-DNA interactions and helix-to-helix and helix-to-coil transitions of nucleic acids.     

Soil volume and carbon storage shifts in drained and afforested wetlands of the Paraná River Delta

Wetland ecosystems have a high carbon storage potential as a result of high primary productivity and low decomposition rates dictated by water saturation. In the herbaceous wetlands of the Paraná River Delta, drainage and afforestation with poplars represents one of the dominant land uses. We explored the effects of these interventions on the volume and carbon storage of the young sedimentary soils of the region. At three sites we identified paired stands occupying similar landscape positions and soil types but subject to natural flooding and covered by natural herbaceous communities or drainage and flood control by dikes and covered by poplar plantations established 12, 17 and 19 years ago. Soil sampling at these sites revealed a reduction of the litter compartment (?86 %) and decreasing volume and porosity of its underlying mineral layer (0–10 cm in the wetland reduced to 0–4 cm in the plantation). Our comparisons of carbon storage accounted for these volumetric shifts by using accumulated mineral mass rather than depth as a reference, showing that tree plantations gained in the mineral soil (22 Mg C ha^?1) almost as much as what they lost in the litter. These gains were particularly large at intermediate depths (4–43 cm in the plantations) were soil porosity remained unaffected and C was raised by 64 % explained by (1) the pulse of inputs from overlaying litter and organic layers subject to rapid decomposition and mobilization after drainage and (2) root colonization, since tree plantations had 75 % of their fine root biomass at these intermediate soil depths, whereas roots in the wetlands did not explore the mineral soil profile and were completely confined to the organic layer. A neutral C balance following wetland drainage and afforestation resulted from the opposing effects of aeration, favoring decomposition in the organic layer, root colonization and organic matter stabilization, favoring its accumulation in the mineral soil.     

Variation of protein binding cavity volume and ligand volume in protein–ligand complexes

We have systematically analyzed the variation of protein binding cavity volume of 200 protein–ligand complexes belonging to eight protein families. Wide variation in protein binding cavity volume for the same protein is observed on binding different ligands. Analysis of individual protein families shows high correlation between atom–atom interactions in binding site and ligand volume. This study implies the significance of protein flexibility in docking small molecule inhibitors on the basis of protein binding cavity volume with respect to ligand volume.     

Proteins in the nervous system — structure and function : Progress in clinical and biological research; volume 79

We have purified a unique enzyme, α-amino-?-caprolactam racemase 945-fold from an extract of Achromobacter obae by Octyl—Sepharose CL-4B and Thiopropyl—Sepharose 6B and some other chromatographies. The purified enzyme was found homogeneous by sodium dodecyl sulfate—polyacrylamide gel electrophoresis and analytical ultracentrifugation. The enzyme has a monomeric structure with M_r ～ 50 000 and a sedimentation coefficient (s_20,w) of 4.28 S. The enzyme contains pyridoxal 5'-phosphate as a coenzyme. The pH optimum for the enzyme activity is ～9.0. D- and L-α-amino-?-caprolactams are the only substrates. The K_m values for the D- and L-isomers are, 8 and 6 mM, respectively.     

How thick is the layer of thermal volume surrounding the protein?

Investigation on the volume properties of protein hydration layers is reported. Presented results are based on combination of Monte Carlo modeling and available experimental data. Six globular proteins with known data are chosen for analysis. Analyzing the model and the experimental results we found that water molecules bound to proteins by hydrogen bond are preferentially located at the places with local depressions on the protein surface. Consequently, the hydration level is not strictly proportional to the area of charged and polar surfaces, but also depends on the shape of the molecular surface. The thickness of the thermal volume layer as calculated in the framework of the scaled particle theory is 0.6-0.65 A for chosen proteins. The obtained value is significantly lower than that presented for proteins in earlier papers (where proportionality between the hydration level and the area of charged and polar surfaces was assumed), but is close to the value published for small solute molecules. Discussion including the influence of protein size and the thermal motion of the surface is presented.     

Phase transitions in nuclei and chromatin. Is nuclear volume controlled by the chromatin or by the nuclear matrix?

Changes in the volume of rat liver nuclei have been monitored as a function of modifications in ionic environment (from 0 to 20 mM), temperature (from 4 to 37 degrees C), and pH (from 1 to 8). An abrupt reduction of nuclear volume occurred with increasing ion concentration, this contraction being more pronounced with bivalent (either Ca2+ or Mg2+) than with monovalent (either Na+ or K+) cations. The lowering of pH produced a similar effect. Parallel changes in chromatin structure took place at the same time as phase-like transitions. Atomic absorption spectroscopy allowed determination of free and nuclei-bound ions, pointing to the presence of a sizeable number of free binding sites for chromatin-DNA even within intact nuclei. DNA-phosphate sites appear to be neutralized by ions strictly according to the size of the electric charge and polyelectrolyte theory. Partial digestion (by micrococcal nuclease) or simple breaks (by chemical carcinogens) of the chromatin-DNA fiber caused respectively elimination or reduction of the abrupt volume changes in the intact nuclei. The apparent role of chromatin structure versus nuclear matrix in determining the shape and volume of intact nuclei is briefly discussed.     

Involvements of the ABC protein ABCF2 and α-actinin-4 in regulation of cell volume and anion channels in human epithelial cells

After osmotic swelling, cell volume is regulated by a process called regulatory volume decrease (RVD). Although actin cytoskeletons are known to play a regulatory role in RVD, it is not clear how actin‐binding proteins are involved in the RVD process. In the present study, an involvement of an actin‐binding protein, α‐actinin‐4 (ACTN4), in RVD was examined in human epithelial HEK293T cells. Overexpression of ACTN4 significantly facilitated RVD, whereas siRNA‐mediated downregulation of endogenous ACTN4 suppressed RVD. When the cells were subjected to hypotonic stress, the content of ACTN4 increased in a 100,000 × g pellet, which was sensitive to cytochalasin D pretreatment. Protein overlay assays revealed that ABCF2, a cytosolic member of the ABC transporter superfamily, is a binding partner of ACTN4. The ACTN4‐ABCF2 interaction was markedly enhanced by hypotonic stimulation and required the NH₂‐terminal region of ABCF2. Overexpression of ABCF2 suppressed RVD, whereas downregulation of ABCF2 facilitated RVD. We then tested whether ABCF2 has a suppressive effect on the activity of volume‐sensitive outwardly rectifying anion channel (VSOR), which is known to mediate Cl^? efflux involved in RVD, because another ABC transporter member, CFTR, was shown to suppress VSOR activity. Whole‐cell VSOR currents were largely reduced by overexpression of ABCF2 and markedly enhanced by siRNA‐mediated depletion of ABCF2. Thus, the present study indicates that ACTN4 acts as an enhancer of RVD, whereas ABCF2 acts as a suppressor of VSOR and RVD, and suggests that a swelling‐induced interaction between ACTN4 and ABCF2 prevents ABCF2 from suppressing VSOR activity in the human epithelial cells. J. Cell. Physiol. 227: 3498–3510, 2012. © 2012 Wiley Periodicals, Inc.     

Requirement of Cl− and Na+ for the ouabain-resistant control of cell volume in slices of rat liver

Summary The ability of liver cells to control their volume in the presence of ouabain has been studied in tissue slices that were recovering at 38°C from a period of swelling at 1°C. Morphological observations were made in conjunction with measurements of the net movements of water and ions. Extrusion of water in the presence of ouabain (2mm) was accompanied by a net loss of Na⁺ and Cl^– and by the formation of characteristic, rounded vesicles in the peri-canalicular regions of the hepatocytes; bile canaliculi were patent. When incubation was carried out in a medium in which either NO ₃ ^– or SO ₄ ^2– replaced Cl^–, ouabain-resistant water extrusion was prevented and the cytoplasmic vesicles normally found with ouabain were almost totally absent. When these slices were subsequently transferred to Cl^– medium with oubain, extrusion of intracellular water was initiated and cytoplasmic vesicles reappeared. Replacement of medium Na⁺ by Li⁺ mimicked the effects of ouabain on water and ion movements and ultrastructure. In addition, the ouabain-resistant extrusion of water and Cl^– was reduced and there was some diminution in the number of vesicles induced by ouabain. Furosemide (2mm) had little effect on water movement or ultrastructure in the absence of ouabain, but it slowed the net water loss and substantially reduced the formation of cytoplasmic vesicles in the presence of ouabain. The results show a close relationship between ouabain-resistant water extrusion and the formation of the cytoplasmic vesicles that are characteristic of treatment with ouabain. They further suggest that a cotransport of Na⁺ and Cl^– forms an important part of the mechanism underlying ouabain-resistant water extrusion and, specifically, that this cotransport may take place across the membranes of the cytoplasmic vesicles.     

Micropylar exudates in Douglas fir – timing and volume of production

 In Pseudotsuga menziesii, a secretion fills the micropylar canal about 7 weeks postpollination until fertilization. Micropylar volumes were measured and found to show variation. Dissection of the ovuliferous scales caused excess fluid to be exuded from the micropylar canal, forming a drop at the tip of the micropyle. This drop was collected, and its production quantified in three trees. Volume and percentage of ovules with drops were greatest when the archegonia in the female gametophyte were at central cell and/or egg cell stage. The volume of exuded drops far exceeded that of the micropyle. Production of subsequent drops by the ovules further confirms that the fluid is actively produced upon dissection Received: 19 September 1998 / Revision accepted: 26 October 1998     

Volume changes and electrostriction in the primary photoreactions of various photosynthetic systems: estimation of dielectric coefficient in bacterial reaction centers and of the observed volume changes with the Drude–Nernst equation

Photoacoustics (PA) allows the determination of enthalpy and volume changes of photoreactions in photosynthetic reaction centers on the 0.1–10 μs time scale. These include the bacterial centers from Rb. sphaeroides, PS I and PS II centers from Synechocystis and in whole cells. In vitro and in vivo PA data on PS I and PS II revealed that both the volume change (–26 A³) and reaction enthalpy (–0.4 eV) in PS I are the same as those in the bacterial centers. However the volume change in PS II is small and the enthalpy far larger, –1 eV. Assigning the volume changes to electrostriction allows a coherent explanation of these observations. One can explain the large volume decrease in the bacterial centers with an effective dielectric coefficient of ∼4. This is a unique approach to this parameter so important in estimation of protein energetics. The value of the volume contraction for PS I can only be explained if the acceptor is the super- cluster (Fe₄S₄)(Cys₄) with charge change from –1 to –2. The small volume change in PS II is explained by sub-μs electron transfer from Y_Z anion to P₆₈₀ cation, in which charge is only moved from the Y_Z anion to the Q_A with no charge separation or with rapid proton transfer from oxidized Y_Z to a polar region and thus very little change in electrostriction. At more acid pH equally rapid proton transfer from a neighboring histidine to a polar region may be caused by the electric field of the P₆₈₀ cation. This revised version was published online in June 2006 with corrections to the Cover Date.     

Changes in dialysate concentrations of glutamate and GABA in the brain: an index of volume transmission mediated actions?

Brain microdialysis has become a frequently used method to study the extracellular concentrations of neurotransmitters in specific areas of the brain. For years, and this is still the case today, dialysate concentrations and hence extracellular concentrations of neurotransmitters have been interpreted as a direct index of the neuronal release of these specific neurotransmitter systems. Although this seems to be the case for neurotransmitters such as dopamine, serotonin and acetylcholine, the extracellular concentrations of glutamate and GABA do not provide a reliable index of their synaptic exocytotic release. However, many microdialysis studies show changes in extracellular concentrations of glutamate and GABA under specific pharmacological and behavioural stimuli that could be interpreted as a consequence of the activation of specific neurochemical circuits. Despite this, we still do not know the origin and physiological significance of these changes of glutamate and GABA in the extracellular space. Here we propose that the changes in dialysate concentrations of these two neurotransmitters found under specific treatments could be an expression of the activity of the neurone-astrocyte unit in specific circuits of the brain. It is further proposed that dialysate changes of glutamate and GABA could be used as an index of volume transmission mediated actions of these two neurotransmitters in the brain. This hypothesis is based firstly on the assumption that the activity of neurones is functionally linked to the activity of astrocytes, which can release glutamate and GABA to the extracellular space; secondly, on the existence of extrasynaptic glutamate and GABA receptors with functional properties different from those of GABA receptors located at the synapse; and thirdly, on the experimental evidence reporting specific electrophysiological and neurochemical effects of glutamate and GABA when their levels are increased in the extracellular space. According to this concept, glutamate and GABA, once released into the extracellular compartment, could diffuse and have long-lasting effects modulating glutamatergic and/or GABAergic neurone-astrocytic networks and their interactions with other neurotransmitter neurone networks in the same areas of the brain.     

Does the presence of arbuscular mycorrhizal fungi influence growth and nutrient uptake of a wild-type tomato cultivar and a mycorrhiza-defective mutant, cultivated with roots sharing the same soil volume?

We investigated the growth and nutrient uptake of the Lycopersicon esculentum symbiosis mycorrhiza-defective plant mutant rmc, challenged with arbuscular mycorrhiza (AM) fungal propagules, in the presence or absence of roots of the commercial wild-type tomato cv. Golden Queen (GQ). Two plants shared the middle (combi) compartment of a horizontal three-compartment split-root pot with one part of their root system; the other part was grown separately in an outer (solo) pot. Combinations of rmc and GQ plants were grown together in soil that was either mycorrhiza-free (-M) or prepared with AM fungal inoculum (+M). Surface colonization of rmc roots was strongly increased in the presence of (+M) GQ roots. AM fungal inoculation increased phosphorus uptake of GQ plants, but decreased growth and P uptake of rmc plants. Growth and P uptake of (+M) GQ plants were reduced when plants were grown in combination with rmc rather than another GQ plant. AM fungi in the (combi) compartment may have preferentially formed hyphae spreading infection rather than functioning in P uptake in (+M) GQ plants grown in combination with rmc. Surface colonization of (+M) rmc roots, in the presence of GQ roots, was probably established at the expense of carbohydrates from associated GQ plants. Possible reasons for a decreased P uptake of rmc plants in response to AM fungal inoculation are proposed.     

Does delivery volume of family physicians predict maternal and newborn outcome?

Background

The number of births attended by individual family physicians who practice intrapartum care varies. We wanted to determine if the practice–volume relations that have been shown in other fields of medical practice also exist in maternity care practice by family doctors.

Methods

For the period April 1997 to August 1998, we analyzed all singleton births at a major maternity teaching hospital for which the family physician was the responsible physician. Physicians were grouped into 3 categories on the basis of the number of births they attended each year: fewer than 12, 12 to 24, and 25 or more. Physicians with a low volume of deliveries (72 physicians, 549 births), those with a medium volume of deliveries (34 physicians, 871 births) and those with a high volume of deliveries (46 physicians, 3024 births) were compared in terms of maternal and newborn outcomes. The main outcome measures were maternal morbidity, 5-minute Apgar score and admission of the baby to the neonatal intensive care unit or special care unit. Secondary outcomes were obstetric procedures and consultation patterns.

Results

There was no difference among the 3 volume cohorts in terms of rates of maternal complications of delivery, 5-minute Apgar scores of less than 7 or admissions to the neonatal intensive care unit or the special care unit, either before or after adjustment for parity, pregnancy-induced hypertension, diabetes, ethnicity, lone parent status, maternal age, gestational age, newborn birth weight and newborn head circumference at birth. High- and medium-volume family physicians consulted with obstetricians less often than low-volume family physicians (adjusted odds ratio [OR] 0.586 [95% confidence interval, CI, 0.479–0.718] and 0.739 [95% CI 0.583–0.935] respectively). High- and medium-volume family physicians transferred the delivery to an obstetrician less often than low-volume family physicians (adjusted OR 0.668 [95% CI 0.542–0.823] and 0.776 [95% CI 0.607–0.992] respectively). Inductions were performed by medium-volume family physicians more often than by low-volume family physicians (adjusted OR 1.437 [95% CI 1.036–1.992].

Interpretation

Family physicians'' delivery volumes were not associated with adverse outcomes for mothers or newborns. Low-volume family physicians referred patients and transferred deliveries to obstetricians more frequently than high- or medium-volume family physicians. Further research is needed to validate these findings in smaller facilities, both urban and rural.More than 20 years ago, Luft and associates¹ conducted one of the earliest volume–outcome studies. Since then, many studies addressing the relation between volume of procedures and patient outcomes have been published.^2,3 In some of these studies, either the hospital size or the physician procedural volume was used as a surrogate for physician expertise. Among studies analyzing hospital volumes and outcomes, better outcomes have been associated with higher patient volumes in some instances^4,5,6,7 but not others.^3,8,9 Some studies of individual provider volume have shown a positive relation between volume and outcomes,^10,11 whereas others have shown no relation or inconsistent results.^3,12 Finally, a few studies analyzing both hospital volume and provider volume have reported a positive volume–outcome relation.^13,14Criticism levelled at the methods used in volume–outcome studies have addressed the lack of adjustment for case mix, different cutoff points for volume categories and retrospective design.³ Other factors that have an effect on patient outcomes but that have not been included in previous volume analyses include health maintenance organization status, physician certification and years since graduation, and patient socioeconomic status, age and ethnicity. Furthermore, most of the studies on volume have covered surgical or oncology specialities.The few studies that have been done on volume and outcome in maternity care have shown variable effects. Rural health care is often associated with lower volumes of obstetric procedures. However, no differences in maternal or newborn outcomes have been shown in some comparisons of births in urban and rural locations.^15,16,17,18 Other studies have shown poorer maternal and newborn outcomes in low-volume hospitals, neonatal intensive care units (NICUs) and rural locations.^19,20,21,22 Conversely, higher volume (hospitals with more than 1000 deliveries per year) has been associated with more maternal lacerations or complications.²³When the health care provider has been the unit of analysis, a relation between volume and maternal or newborn outcome has been demonstrated in at least one study²⁴ but not in others.^25,26 Low volume has been defined as 20 to 24 deliveries per year.^24,26 Hass and colleagues²⁴ reported an adjusted odds ratio (OR) of 1.4 for low birth weight for infants delivered by low-volume non-board-certified physicians relative to high-volume non-board-certified physicians; the adjusted OR was 1.56 for low-volume board-certified physicians relative to high-volume board-certified physicians (98.7% of whom were obstetricians).Possible explanations for the differences among studies include differences in health care delivery systems, insurance coverage, experience and training of providers, maternal risk factors, triage or transfer of high-risk cases, choice of outcome measures, and changes over time in access to care, quality assurance and standard of living. Relations have been reported between maternal or newborn outcomes and smoking, maternal history of low birth weight (for previous pregnancies), pregnancy–induced hypertension, diabetes, prepregnancy weight, gestational weight gain, maternal height and age, multiple gestation, previous vaginal birth after cesarean section, history of previous delivery problems, parity, large-for-date fetus, ethnicity and fetal sex.^25,27,28,29 Few studies of the relation between volume of births and obstetric outcome have been able to control for these potentially confounding variables and adjust for maternal risk factors.Our database of detailed accounts of births in one hospital setting allowed us to examine this issue more rigorously. We posed 2 research questions: Is there a relation between the volume of deliveries attended by individual family physicians and maternal and newborn outcomes? If there are differences in outcomes, are they related to different physician practice styles and consultation patterns?     

A comparison of pressure–volume curves with and without rehydration pretreatment in eight woody species of the semiarid Loess Plateau

Pressure–volume (P–V) curves are frequently used to analyze water relation properties of woody plants in response to transpiration-induced tissue water loss. In this study, P–V analyses were conducted on eight woody species growing in the semiarid Loess Plateau region of China during a relatively dry summer season using both the recently recommended instantaneous measurement and the traditional method with rehydration pretreatment. Generally, P–V-derived parameters in this study reflected conditions in a dry growth environment. Species-specific differences were also found among P–V parameters, suggesting each species uses different mechanisms to respond to drought. Based on the results from instantaneous measurements, a descending sequence for drought tolerance ranked by water potentials at the turgor loss point (Ψ^tlp) was Rosa hugonis > Syringa oblata = Armeniaca sibirica > Caragana microphylla > Pyrus betulaefolia > Acer stenolobum > Quercus liaotungensis > Robinia pseudoacacia. The first five species also showed lower levels of osmotic potential at full turgor (Ψ _π ^sat ) and higher symplastic osmotic solute content per dry weight, suggesting they possess advantages in osmotic adjustment. Also, this study supports previous reports noting rehydration pretreatment resulted in shifts in P–V parameters. The magnitude of the shifts varied with species and water conditions. The effect of rehydration was stronger for species with higher drought tolerance or subjected to the influence of drought. Differences in the parameters among species were mitigated as a result of rehydration. Those with a lower Ψ^tlp or midday water potential were more deeply affected by rehydration. Application of instantaneous measurements was strongly recommended for proper analysis of P–V curves particularly in arid and semiarid areas.     

Technical note: Mapping of trabecular bone anisotropy and volume fraction in 3D using μCT images of the human calcaneus

Trabecular bone anisotropy, describing preferential trabecular co-alignment, is a proxy for its long-term loading history. Trabecular anisotropy varies locally, thus rendering averaged calculations across an entire bone inutile. Here we present a 3D trabecular anisotropy mapping method using vector fields where each vector reflects the extent of local co-alignment of the elementary units of surface. 3D anisotropy maps of hundreds of thousands of vectors were visualized by their magnitude and direction. Similarly, volume fraction was mapped as 3D scalar fields. We constructed anisotropy and volume fraction maps using micro-computed tomography of four presumably nonpathologic human calcanei and compared their anisotropy signature with pathologically loaded calcanei in club foot and calcaneonavicular ankylosis. In the nonpathologic calcaneus, a pattern of four anisotropy trajectories (bands) was consistently identified as dorsal, plantar, Achilles', and peroneal bands. Both pathologic specimens deviated from the nonpathologic maps. The calcaneus in the congenitally disused club foot showed very low local anisotropy values, no co-oriented bands, and low volume fraction. The ankylosed calcaneus showed lower anisotropy than the nonpathologic calcaneus, but not to the same extent as the club foot, and showed patchy high volume fraction. The directionality of co-oriented bands was barely discernable in the ankylosed calcaneus as compared to nonpathologic calcaneus. The anisotropy signature of the nonpathologic calcaneus is consistent with a kinetic loading pattern attributable to walking. The loss of this kinetic loading results in an absent/vanishing anisotropy signature. Such 3D mapping adds new dimensions to quantitative bioimaging of bone and the understanding of skeletal adaptation.     

Clarifying the influence of core amino acid hydrophobicity, secondary structure propensity, and molecular volume on amyloid-β 16-22 self-assembly

The self-assembly of amyloid peptides is influenced by hydrophobicity, charge, secondary structure propensity, and sterics. Previous experiments have shown that increasing hydrophobicity at the aromatic positions of the amyloid-β 16-22 fragment (Aβ(16-22)) without introducing steric restraints greatly increases the rate of self-assembly and thermodynamically stabilizes the resulting fibrils [Senguen et al., Mol. BioSyst., 2011, DOI: 10.1039/c0mb00080a]. Conversely, when increasing side chain hydrophobicity coincides with an increase in side chain volume, the increase in the rate of self-assembly is offset by a thermodynamic destabilization of the resulting amyloid fibrils when direct cross-strand side chain interactions occur. These findings indicate that steric effects also influence the self-assembly of amyloidogenic peptides. Herein, the aromatic Phe residues at positions 19, 20, and 19,20 of Aβ(16-22) have been systematically replaced by Val, Leu, Ile, or hexafluoroleucine (Hfl) and amyloid formation has been characterized. The Val variants, despite the high β-sheet propensity of Val, were thermodynamically destabilized (ΔΔG = +0.1-0.4 kcal mol(-1)) relative to the wild-type with the double mutant failing to self-assemble at the concentrations studied. Conversely, the Leu and Ile variants formed fibrils at enhanced rates relative to wild-type and exhibited similar, or in some cases enhanced thermodynamic stabilities relative to the wild-type (ΔΔG = 0-0.6 kcal mol(-1)). The more hydrophobic Hfl variants were greatly stabilized (ΔΔG = -0.3-2.1 kcal mol(-1)) relative to the wild-type. These data indicate that hydrophobicity and steric effects both influence peptide self-assembly processes, including nucleation and fibrillization rates and the thermodynamic stability of the resulting fibrils.